GCS overexpression is associated with multidrug resistance of human HCT-8 colon cancer cells

<p>Abstract</p> <p>Purpose</p> <p>Multidrug resistance is one of the main impediments to the successful treatment of colon cancer. Glucosylceramide synthase (GCS) which is related to multidrug resistance (MDR) can reduce the level of ceramide and can help cells escape from the ceramide-induced cell apoptosis. However, the underlying mechanism is still unclear.</p> <p>Methods</p> <p>The cell proliferation and cell toxicity were measured with Cell Counting Kit-8 (CCK-8). The mRNA levels of GCS and MDR1 were detected by semiquantitative reverse transcription-PCR amplification, the protein levels of GCS, caspase-3 and P-gp proteins were indicated by Western blotting. The apoptosis rates of cells were measured with flow cytometry.</p> <p>Results</p> <p>The relative mRNA levels of GCS in HCT-8, HCT-8/VCR, HCT-8/VCR- sh-mock and HCT-8/VCR-sh-GCS were 71.4 ± 1.1%, 95.1 ± 1.2%, 98.2 ± 1.5%, and 66.6 ± 2.1% respectively. The mRNA levels of MDR1 were respectively 61.3 ± 1.1%, 90.5 ± 1.4%, 97.6 ± 2.2% and 56.1 ± 1.2%. The IC50 of Cisplatin complexes were respectively 69.070 ± 0.253 μg/ml, 312.050 ± 1.46 μg/ml, 328.741 ± 5.648 μg/ml, 150.792 ± 0.967 μg/ml in HCT-8, HCT-8/VCR, HCT-8/VCR-sh-mock and HCT-8/VCR-sh-GCS. The protein levels of caspase-3 were 34.2 ± o.6%, 93.0 ± 0.7%, 109.09 ± 0.7%, 42.7 ± 1.3% respectively. The apoptosis rates of cells were 8.77 ± 0.14%, 12.75 ± 0.54%, 15.39 ± 0.41% and 8.49 ± 0.23% respectively.</p> <p>Conclusion</p> <p>In conclusion, our research indicated that suppression of GCS restores the sensitivity of multidrug resistance colon cancer cells to drug treatment.</p

Reversible manipulation of the magnetic state in SrRuO3 through electric-field controlled proton evolution

Ionic substitution forms an essential pathway to manipulate the structural phase, carrier density and crystalline symmetry of materials via ion-electron-lattice coupling, leading to a rich spectrum of electronic states in strongly correlated systems. Using the ferromagnetic metal SrRuO3 as a model system, we demonstrate an efficient and reversible control of both structural and electronic phase transformations through the electric-field controlled proton evolution with ionic liquid gating. The insertion of protons results in a large structural expansion and increased carrier density, leading to an exotic ferromagnetic to paramagnetic phase transition. Importantly, we reveal a novel protonated compound of HSrRuO3 with paramagnetic metallic as ground state. We observe a topological Hall effect at the boundary of the phase transition due to the proton concentration gradient across the film-depth. We envision that electric-field controlled protonation opens up a pathway to explore novel electronic states and material functionalities in protonated material systems

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial

Background: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792. Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial (vol 26, 46, 2022)

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Analysis of short-term outcome indicators and risk factors for postoperative complications in patients with sigmoid colon cancer by transumbilical single-port plus one port laparoscopy

This study aimed to compare the efficacy of Single-Port plus One Port Laparoscopy (SILS + 1) with Conventional Multi-Port Laparoscopic Surgery (CLS) and investigate risk factors associated with postoperative complications in patients with sigmoid colon cancer undergoing laparoscopy. Male patients with sigmoid colon cancer treated at our hospital were selected and evenly distributed into the CLS and SILS + 1 groups and further categorized into complication and non-complication groups based on their complications status within 30 days post-surgery. Compared to the CLS group, the SILS + 1 group had significantly shorter incision length, greater distance to the lower edge of the tumor and shorter time to first postoperative ambulation (p < 0.05). A total of 20 cases (16.67%) developed complications within 30 days post-surgery, and among them, 8 (13.33%) were in the SILS + 1 group and 12 (20.00%) in the CLS group (p = 0.327). Logistic multivariable regression analysis showed that age (p = 0.028; Odds Ratio (OR) = 1.028; 95% confidence interval (CI): 1.003–1.054), body mass index (BMI) (p = 0.002; OR = 1.950; 95% CI: 1.248–2.961) and operation time (p < 0.001; OR = 1.067; 95% CI: 1.030–1.106) were independent risk factors for complication occurrence within 30 days post-surgery, and at 2-year follow-up, there was no significant difference in overall survival between both groups (p > 0.05). In conclusion, age, BMI and duration of surgery were identified as independent risk factors for postoperative complications in male sigmoid colon cancer patients, among whom SILS + 1 was found to reduce postoperative discomfort and accelerate recovery compared to CLS while maintaining surgical efficacy

Drug-eluting stents for acute coronary syndrome: a meta-analysis of randomized controlled trials.

Drug-eluting stents (DES) are increasingly used for treatment of acute coronary syndrome (ACS). However, clinical efficacy and safety of various types of DES is not well established in these subjects. We therefore evaluated clinical utility of second-generation and first-generation DES in patients with ACS by conducting a meta-analysis.A search of Medline, Embase, the Cochrane databases, and Web of Science was made. Randomized controlled trials (RCTs) which compared second-generation DES (everolimus-eluting stents [EES] or zotarolimus-eluting stents [ZES]) versus first-generation DES (sirolimus-eluting stents [SES] or paclitaxe-eluting stents [PES]) in patients with ACS and provided data on clinical efficacy or safety endpoints were included. Pooled estimates were calculated using random-effects model.A total of 2,757 participants with ACS in 6 RCTs were included. Compared with first-generation one, second-generation DES trended to be associated with the decreased incidence of definite or probable stent thrombosis in ACS patients (risk ratio [RR]  = 0.60, 95% confidence intervals [CI] 0.33 to 1.07, p = 0.09). However, the rate of target lesion revascularization (TLR) significantly increased in second-generation DES (RR = 2.08, 95%CI 1.25 to 3.47, p = 0.005). There were no significant differences in the incidence of major adverse cardiac events (MACEs), all-cause death, cardiac death, and recurrent myocardial infarction between the two arms (all p>0.10). The second-generation EES showed a tendency towards lower risk of MACEs (p = 0.06) and a beneficial effect on reducing stent thrombosis episodes (p = 0.009), while the second-generation ZES presented an increased occurrence of MACEs (p = 0.02) and TLR (p = 0.003).Second-generation DES, especially EES, appeared to present a lower risk of stent thrombosis, whereas second-generation ZES might increase the need for repeat revascularization in ACS patients. During coronary interventional therapy, DES class should be adequately considered in order to maximize clinical benefit of DES implantation in these specific subjects

Analysis of the Formation Mechanism of Secondary Tip Leakage Vortex (S-TLV) in an Axial Flow Pump

Studies on the tip leakage vortex (TLV) are extensive, while studies on the secondary tip leakage vortex (S-TLV) are rare. To advance the understanding of the formation mechanism of the S-TLV, turbulent cavitating flows were numerically investigated using the shear stress transport (SST) turbulence model and the Zwart–Gerber–Belamri cavitation model. The morphology and physical quantity distribution of the S-TLV under two cavitation conditions were compared, and its formation mechanism was analyzed. The results reveal that in the lower cavitation number case, there is a low-velocity zone of circumferential flow near the tip in the back half of the blade. The shear vortices formed by the leakage jet gradually accumulate and concentrate in the low-velocity area, which is one of the main sources of the S-TLV. Meanwhile, the radial jet pushes the vortices on the suction surface to the tip, which mixes with the S-TLV. The flow path formed by the radial jet and the leakage jet is in accordance with the rotation direction of the S-TLV, which promotes the S-TLV’s further development. Under the conditions of a small cavitation number and low flow rate, the circumferential velocity and radial velocity of the fluid near the gap have altered significantly, which is conducive to the formation of the S-TLV

Numerical Analysis of the Effect of Cavitation on the Tip Leakage Vortex in an Axial-Flow Pump

To understand the effect of cavitation on the tip leakage vortex (TLV), turbulent cavitating flows were numerically investigated using the shear-stress transport (SST) k–ω turbulence model and the Zwart–Gerber–Belamri cavitation model. In this work, two computations were performed—one without cavitation and the other with cavitation—by changing the inlet pressure of the pump. The results showed that cavitation had little effect on the pressure difference between the blade surfaces for a certain cavitation number. Instead, it changed the clearance flow and TLV vortex structure. Cavitation caused the TLV core trajectory to be farther from the suction surface and closer to the endwall upstream of the blade. Cavitation also changed the vortex strength distribution, making the vortex more dispersed. The vortex flow velocity and turbulent kinetic energy were lower, and the pressure pulsation was more intense in the cavitating case. The vorticity transport equation was used to further analyze the influence of cavitation on the evolution of vortices. Cavitation could change the vortex stretching term and delay the vortex bending term. In addition, the vortex dilation term was drastically changed at the vapor–liquid interface