Secretory Leukocyte Protease Inhibitor Binds to Annexin II, a Cofactor for Macrophage HIV-1 Infection

The distribution of secretory leukocyte protease inhibitor (SLPI) at entry portals indicates its involvement in defending the host from pathogens, consistent with the ability of SLPI to inhibit human immunodeficiency virus (HIV)-1 infection by an unknown mechanism. We now demonstrate that SLPI binds to the membrane of human macrophages through the phospholipid-binding protein, annexin II. Based on the recent identification of human cell membrane phosphatidylserine (PS) in the outer coat of HIV-1, we define a novel role for annexin II, a PS-binding moiety, as a cellular cofactor supporting macrophage HIV-1 infection. Moreover, this HIV-1 PS interaction with annexin II can be disrupted by SLPI or other annexin II–specific inhibitors. The PS–annexin II connection may represent a new target to prevent HIV-1 infection

The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in vitro and in vivo

AbstractSupranutritional selenite has anti-cancer therapeutic effects in vivo; however, the detailed mechanisms underlying these effects are not clearly understood. Further studies would broaden our understanding of the anti-cancer effects of this compound and provide a theoretical basis for its clinical application. In this study, we primarily found that selenite exposure inhibited phosphorylation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), leading to suppression of Bcl-2 in HCT116 and SW480 colorectal cancer (CRC) cells. Moreover, the selenite-induced inhibitory effect on PKD1 activation was involved in suppression of the CREB signalling pathway. Additionally, we discovered that selenite treatment can upregulate p38 MAPK phosphorylation, which results in inhibition of the PKD1/CREB/Bcl-2 survival pathway and triggers apoptosis. Finally, we established a colorectal cancer xenograft model and found that selenite treatment markedly inhibits tumour growth through the MAPK/PKD1/CREB/Bcl-2 pathway in vivo. Our results demonstrated that a supranutritional dose of selenite induced CRC cell apoptosis through inhibition of the PKD1/CREB/Bcl-2 axis both in vitro and in vivo

Lantern-shaped screw loaded with autologous bone for treating osteonecrosis of the femoral head

Background: Treatment for osteonecrosis of the femoral head (ONFH) in young individuals remains controversial. We developed a lantern-shaped screw, which was designed to provide mechanical support for the femoral head to prevent its collapse, for the treatment of ONFH. The purpose of this study was to investigate the efficacy and safety of the lantern-shaped screw loaded with autologous bone for the treatment of pre-collapse stages of ONFH. Methods: Thirty-two patients were randomly divided into two groups: the lantern-shaped screw group (core decompression and lantern-shaped screw loaded with autogenous bone) and the control group (core decompression and autogenous bone graft). During 36 months follow-up after surgery, treatment results in patients were assessed by X-ray and computed tomography (CT) scanning as well as functional recovery Harris hip score (HHS). Results: Successful clinical results were achieved in 15 of 16 hips (94%) in the lantern-shaped screw group compared with 10 of 16 hips (63%) in the control group (p = 0.0325). Successful radiological results were achieved in 14 of 16 hips (88%) in the lantern-shaped screw group compared with 8 of 16 hips (50%) in the control group (P = 0.0221). Conclusion: The lantern-shaped screw loaded with autologous bone for the treatment of pre-collapse stages of ONFH is effective and results in preventing progression of ONFH and reducing the risk of femoral head collapse

Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo

BACKGROUND: Previous studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells have not been demonstrated. METHODS: The toxic effect of selenite on leukemic HL60 cells was performed with cell counting kit 8. Selenite effects on cell cycle distribution and apoptosis induction were determined by flow cytometry. The contents of cyclin B1, Mcl-1, AIF, cytochrome C, insoluble and soluble tubulins were detected with western blotting. Microtubules were visualized with indirect immunofluorescence microscopy. The interaction between CDK1 and Mcl-1 was assessed with immunoprecipitation. Decreasing Mcl-1 and cyclin B1 expression were carried out through siRNA interference. The alterations of Mcl-1 and cyclin B1 in animal model were detected with either immunohistochemical staining or western blotting. In situ detection of apoptotic ratio was performed with TUNEL assay. RESULTS: Our current results showed that selenite inhibited the growth of HL60 cells and induced mitochondrial-related apoptosis. Furthermore, we found that microtubule assembly in HL60 cells was altered, those cells were arrested at G2/M phase, and Cyclin B1 was up-regulated and interacted with CDK1, which led to down-regulation of the anti-apoptotic protein Mcl-1. Finally, in vivo experiments confirmed the in vitro microtubule disruption effect and alterations in Cyclin B1 and Mcl-1 levels by selenite. CONCLUSIONS: Taken together, the results from our study indicate that microtubules are novel targets of selenite in leukemic HL60 cells

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

Effects of L-Arginine Cardioplegia on Myocardium

Infusion of L-arginine (a precursor of nitric oxide, NO) in cardioplegia was examined to test its effect on metabolism of myocardium after myocardial ischemia and reperfusion (IR). Twenty-eight patients undergoing valve replacement were involved and randomly divided into two groups: the control group (crystalloid cardioplegia) and the experimental group (crystalloid cardioplegia + L-arginine). Blood samples were taken both before aortic clamping and after aortic unclamping from right radial artery to measure the concentrations of NO2−/NO3−, lactic acid (LA), malondialdehyde (MDA), superoxide dismutase (SOD), and xanthine oxidase (XOD). In the control group, the NO2−/NO3− level decreased at aortic unclamping, and 30 min later, it decreased significantly as compared with that before aortic clamping (p < .05). In the experimental group, it increased at aortic unclamping (p < .05), and 60 min later, increased to the peak. Five, fifteen, and thirty min after aortic unclamping, the concentrations of LA and MDA in the experimental group were lower than those in the control group (p < .05). Thirty and sixty min after aortic unclamping, the concentrations of SOD remained higher in the experimental group than those in the control group (p < .05). There was no difference between groups in the concentrations of XOD. The addition of L-arginine to the cardioplegia can protect the myocardium from injury by releasing nitric oxide

The Influences of NO and Ach on cGMP Levels in Two Patient Populations

Pulmonary hypertension following cardiac surgery is an important factor affecting postoperative mortality, and its mechanism has not been thoroughly clarified. Cardiopulmonary bypass (CPB) can destroy pulmonary endothelium and aggravate pulmonary hypertension. This study is designed to investigate the impacts of CPB on vascular endothelium-dependent relaxation, and the relations of CPB to pulmonary hypertension. Forty patients undergoing valve surgery were involved. According to their preoperative pulmonary arterial pressure (PAP), these patients were divided into pulmonary hypertension group (H group) and normal group (N group). The concentrations of cyclic guanosine monophosphate (cGMP) were measured at baseline conditions, after acetylcholine (Ach) injection, and during nitric oxide (NO) inhalation. Samples were taken before sternotomy and after weaning from CPB, 4 and 12 hours post-CPB. At baseline, the level of cGMP in the H group was lower than that of the N group by 33.9% before CPB. After initiating the CPB, although the level of cGMP continuously decreased in both groups until weaning from CPB (the N group decreased 33.3%, and the H group decreased 59%). At that point cGMP was higher in N group than in the H group (p < .01). The level of cGMP of both groups tended to recover 4 hours after CPB, but only the N group returned to baseline 12 hours after CPB. After injection of Ach, the level of cGMP of both groups followed the same change as in the baseline, except with different numeric value. The level of cGMP in N group rose ranging from 160.0–197.3%, while it rose ranging from 87.7–168.1% in H group. The levels of cGMP were higher in N group than those in H group at all times following injection of Ach (61.4, 173.3, 202.7, and 188.0%)(p < .01). After inhalation of NO, the level of cGMP of both groups followed the same change as the baseline. The level of cGMP in N group rose ranging from 194.8–320.5%. Although the levels of cGMP were higher in N group than those in H group (6.9, 25.3, 23.3, and 16.6%), significant differences were achieved at the 4 and 12 hour post-CPB periods (p < .05 or p < .01, respectively). It was concluded that the injury of vascular endothelial function caused by CPB was more critical in pulmonary hypertension patients

Morphological Features-Based Descriptive Index System for Lunar Impact Craters

Lunar impact craters are important for studying lunar surface morphology because they are the most typical morphological units of the Moon. Impact crater descriptive indices can be used to describe morphological features and thus provide direct evidence for both the current state and evolution history of the Moon. Current description methods for lunar impact craters are predominantly qualitative, and mostly focus on their morphological profiles. Less attention is paid to the detailed morphological features inside and outside of the craters. A well-established and descriptive index system is required to describe the real morphological features of lunar impact craters, which are complex in a systematic way, and further improve study, such as heterogeneity analyses of lunar impact craters. This study employs a detailed lunar surface morphological analysis to propose a descriptive index system for lunar impact craters, including indices for the description of individual craters based on their morphological characteristics, spatial structures and basic composition (i.e., crater rim, crater wall, crater floor, central uplift, and ejecta), and indices for crater groups, including spatial distribution and statistical characteristics. Based on the proposed descriptive index system, a description standard for lunar impact craters is designed for categorising and describing these indices in a structured manner. To test their usability and effectiveness, lunar impact craters from different locations are manually detected, and corresponding values for different indices are extracted and organised for a heterogeneity analysis. The results demonstrate that the proposed index system can effectively depict the basic morphological features and spatial characteristics of lunar impact craters