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BackgroundEndoplasmic reticulum (ER) stress is considered one of the mechanisms contributing to reactive oxygen species (ROS)- mediated cell apoptosis. In diabetic cardiomyopathy (DCM), cell apoptosis is generally accepted as the etiological factor and closely related to cardiac ROS generation. ER stress is proposed the link between ROS and cell apoptosis; however, the signaling pathways and their roles in participating ER stress- induced apoptosis in DCM are still unclear.MethodsIn this study, we investigated the signaling transductions in ROS- dependent ER stress- induced cardiomocyte apoptosis in animal model of DCM. Moreover, in order to clarify the roles of IRE1 (inositol - requiring enzyme-1), PERK (protein kinase RNA (PKR)- like ER kinase) and ATF6 (activating transcription factor-6) in conducting apoptotic signal in ROS- dependent ER stress- induced cardiomocyte apoptosis, we further investigated apoptosis in high- glucose incubated cardiomyocytes with IRE1, ATF6 and PERK- knocked down respectively.Resultswe demonstrated that the ER stress sensors, referred as PERK, IRE1 and ATF6, were activated in ROS- mediated ER stress- induced cell apoptosis in rat model of DCM which was characterized by cardiac pump and electrical dysfunctions. The deletion of PERK in myocytes exhibited stronger protective effect against apoptosis induced by high- glucose incubation than deletion of ATF6 or IRE in the same myocytes. By subcellular fractionation, rather than ATF6 and IRE1, in primary cardiomyocytes, PERK was found a component of MAMs (mitochondria-associated endoplasmic reticulum membranes) which was the functional and physical contact site between ER and mitochondria.ConclusionsROS- stimulated activation of PERK signaling pathway takes the major responsibility rather than IRE1 or ATF6 signaling pathways in ROS- medicated ER stress- induced myocyte apoptosis in DCM.

Purpose To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiotherapy (SBRT) of the thorax. Methods Published studies on lung toxicity in patients with early stage non-small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2-5 (G2+) and grade 3-5 (G3+) RILT were computed. Patient, tumor and dosimetric factors were analyzed for their correlation with RILT. Results Eighty-eight studies (7752 patients), that reported RILT incidence, were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% CI: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range 1.4-4.1) cm. Among the factors analyzed, older patient age (P= 0.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P= 0.049) and G3+ RILT (P= 0.001). Patients with stage IA vs. stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, OR= 0.43, 95% CI: 0.29-0.64, P<0.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P= 0.027) and V20 (P= 0.019) in patients with G2+ RILT comparing to that of grade 0-1 RILT. Conclusions The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD also significantly affect RILT risk. Summary Risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiotherapy (SBRT) were analyzed from 88 published studies (7752 patients). The overall rate of RILT is relatively low after thoracic SBRT. Adverse risk factors for RILT after SBRT include older age, larger tumor size and greater lung dose-volume exposure as measured by mean lung dose and volume of lung receiving greater than 20 Gy.

PMTA for fibroid is feasible and safe, and it is an easy and fast procedure that is minimally invasive.

BackgroundThe value of goal-directed fluid therapy in neurosurgical patients, where brain swelling is a major concern, is unknown. The aim of our study was to evaluate the effect of an intraoperative goal-directed fluid restriction (GDFR) strategy on the postoperative outcome of high-risk patients undergoing brain surgery. MethodsHigh-risk patients undergoing brain surgery were randomly assigned to a usual care group (control group) or a GDFR group. In the GDFR group, (1) fluid maintenance was restricted to 3 ml/kg/h of a crystalloid solution and (2) colloid boluses were allowed only in case of hypotension associated with a low cardiac index and a high stroke volume variation. The primary outcome variable was ICU length of stay, and secondary outcomes were lactates at the end of surgery, postoperative complications, hospital length of stay, mortality at day 30, and costs.ResultsA total of 73 patients from the GDFR group were compared with 72 patients from the control group. Before surgery, the two groups were comparable. During surgery, the GDFR group received less colloid (1.9 ± 1.1 vs. 3.9 ± 1.6 ml/kg/h, p = 0.021) and less crystalloid (3 ± 0 vs. 5.0 ± 2.8 ml/kg/h, p < 0.001) than the control group. ICU length of stay was shorter (3 days [1–5] vs. 6 days [3–11], p = 0.001) and ICU costs were lower in the GDFR group. The total number of complications (46 vs. 99, p = 0.043) and the proportion of patients who developed one or more complications (19.2 vs. 34.7%, p = 0.034) were smaller in the GDFR group. Hospital length of stay and costs, as well as mortality at 30 day, were not significantly reduced.ConclusionIn high-risk patients undergoing brain surgery, intraoperative GDFR was associated with a reduction in ICU length of stay and costs, and a decrease in postoperative morbidity. Trial registration Chinese Clinical Trial Registry ChiCTR-TRC-13003583, Registered 20 Aug, 2013