Alteration of Innate Immunity by Donor IL-6 Deficiency in a Presensitized Heart Transplant Model

Engraftment of IL-6 deficient donor into wild-type recipient could significantly improve allograft survival through T cell lineage particularly regulatory T cells (Tregs) in non-sensitized transplant host. However, its effect on innate immune responses remains uncertain. Our data revealed that donor IL-6 deficiency significantly increased infiltration of two subsets of MDSCs (CD11b+Gr1+myeloid-derived suppressor cells), CD11b+Gr1-low and CD11b+Gr1-int with strong immunosuppression activity in the transplanted graft. It resulted in a dramatic increase of CD11b+Gr1-low frequency and a significant decrease of the frequency of CD11b+Gr1-high and CD4-CD8-NK1.1+ cells in the recipient’s spleen. Unexpectedly, donor IL-6 deficiency could not significantly reduce macrophage frequency irrespective of in the host’s spleen or graft. Taken together, suppression of innate immune effector cells and enhanced activity of regulatory MDSCs contributed to tolerance induction by blockade of IL-6 signaling pathway. The unveiled novel mechanism of targeting IL-6 might shed light on clinical therapeutic application in preventing accelerated allograft rejection for those pre-sensitized transplant recipients

Vertically-aligned Mn(OH)2 nanosheet films for flexible all-solid-state electrochemical supercapacitors

The arrangement of the electrode materials is a significant contributor for constructing high performance supercapacitor. Here, vertically-aligned Mn(OH)2 nanosheet thin films were synthesized by cathodic electrodeposition technique on flexible Au coated polyethylene terephthalate substrates. Morphologies, microstructures, chemical compositions and valence state of the nanosheet films were characterized systematically. It shows that the nanosheets arranged vertically to the substrate, forming a porous nanowall structures and creating large open framework, which greatly facilitate the adsorption or diffusion of electrolyte ions for faradaic redox reaction. Electrochemical tests of the films show the specific capacitance as high as 240.2 F g−1 at 1.0 A g−1. The films were employed to assemble symmetric all-solid-state supercapacitors with LiCl/PVA gel severed as solid electrolyte. The solid devices exhibit high volumetric capacitance of 39.3 mF cm−3 at the current density 0.3 mA cm−3 with robust cycling stability. The superior performance is attributed to the vertically-aligned configuration

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

Spatial variability of stable isotopes in river water over the Tibetan Plateau

<p>Stable isotopes dataset for the manuscript "Spatial variability of stable isotopes in river water over the Tibetan Plateau". </p> <p>This dataset includes 437 new available isotopic data of river water firstly sampled from May 2013 to July 2016 covering eight great river basins over the TP, including the Upper Ganges, Upper Brahmaputra, Upper Mekong, Upper Salween, Upper Indus, Upper Yangtze, Upper Yellow, and the Endorheic Rivers. River water isotopic date from twelve previous studies are also complied, including 1178 samples with both δ<sup>18</sup>O and δD values, 231 with only δ<sup>18</sup>O values and 6 with only δD values. All data used in this study are accompanied by geographical information.</p&gt

Antihypertensive treatment and risk factors for syncope in asymptomatic aortic stenosis patients with hypertension

Background Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis(AS) is scarce. Objectives Given the paucity of data on the relationship between syncope and antihypertensive treatment in aortic stenosis. This study sought to investigate this association in patients admitted to our hospital. Methods A total of 158 patients with asymptomatic moderate or severe aortic stenosis were analyzed. Follow-up was conducted by clinic visit, telephone contact, or review of electronic medical records. Outcomes were syncope. Results Hypertension were documented in 90 of the 158 patients with moderate or severe AS, and 77 of them received antihypertensive medications. During an average 28 months follow-up period, the occurrence of syncope was observed in 13 patients. Among them, 8 were in antihypertensive group (n = 77) and 5 in normotensive group (n = 68). There was no significant difference in incidence of syncope between the two groups. Patients with treated hypertension and syncope had a lower stroke volume index (SVi), a higher valve arterial impedance (ZVA), a smaller SAC than those without. Kaplan-Meier analysis showed that there was no significant difference in syncope cumulative incidence between antihypertensive group and normotensive group (log rank P = .478). Multivariate cox regression analysis showed that both ZVA (hazard ratio:19.006, 95% confidence interval: 4.664 to77.448;P = .002) and LVMI (hazard ratio:1.484, 95% confidence interval: 1.427 to 5.157;P = .016) were associated with development of syncope, whereas hypertension were not related independently to syncope (hazard ratio:0.935, 95% confidence interval: 0.786 to3.173; P = .869). Conclusions In patients with moderate or severe AS, concomitant hypertension, and antihypertensive treatment didn’t increase the occurrence of syncope, whereas higher ZVA was independently associated with greater risk of syncope

Vertically-aligned Mn(OH)2 nanosheet films for flexible all-solid-state electrochemical supercapacitors

The arrangement of the electrode materials is a significant contributor for constructing high performance supercapacitor. Here, vertically-aligned Mn(OH)2 nanosheet thin films were synthesized by cathodic electrodeposition technique on flexible Au coated polyethylene terephthalate substrates. Morphologies, microstructures, chemical compositions and valence state of the nanosheet films were characterized systematically. It shows that the nanosheets arranged vertically to the substrate, forming a porous nanowall structures and creating large open framework, which greatly facilitate the adsorption or diffusion of electrolyte ions for faradaic redox reaction. Electrochemical tests of the films show the specific capacitance as high as 240.2 F g−1 at 1.0 A g−1. The films were employed to assemble symmetric all-solid-state supercapacitors with LiCl/PVA gel severed as solid electrolyte. The solid devices exhibit high volumetric capacitance of 39.3 mF cm−3 at the current density 0.3 mA cm−3 with robust cycling stability. The superior performance is attributed to the vertically-aligned configuration.</p

Analysis on the Pathogenesis of Symptomatic Pulmonary Embolism with Human Genomics

<p><b>BACKGROUND</b>: In the present study, the whole human genome oligo microarray was employed to investigate the gene expression profile in symptomatic pulmonary embolism (PE).</p><p><b>METHODS</b>: Twenty patients with PE and 20 age and gender matched patients without PE as controls were enrolled into the present study in the same period. The diagnosis of PE was based on the clinical manifestations and findings on imaging examinations. Acute arterial and/or venous thrombosis was excluded in controls. The whole human genome oligo microarray was employed for detection. Statistical analysis was performed with t test following analysis of very small samples of repeated measurements and Gene Ontology (GO) analysis.</p><p><b>RESULTS</b>: Genomic data showed no damage to vascular endothelial cells in PE patients. Genomic data only found increased mRNA expression of a small amount of coagulation factors in PE patients. In the PE group, anticoagulant proteins, Fibrinolytic system and proteins related to platelet functions only played partial roles in the pathogenesis of PE. In addition, the mRNA expressions of a fraction of adhesion molecules were markedly up-regulated. Gene Ontology analysis showed the genes with down-regulated expressions mainly explain the compromised T cell immunity. Symptomatic VTE patients have compromised T cell immunity.</p><p><b>CONCLUSION: </b>The damage to vascular endothelial cells is not necessary in the pathogenesis of VTE, and only a fraction of factors involved in the shared coagulation cascade are activated. Genomic results may provide a new clue for clinical diagnosis, treatment and prevention of VTE.</p

Kaplan-Meier cardiac graft survival curve.

<p>Heterotopic abdominal heart transplantation was performed by using standard procedure. All transplanted mice were monitored every day until graft rejection, defined as the cessation of palpable cardiac activity. Although only three symbols of “triangle” are observed for group (WT B6B/c), two grafts survived for 7 days and two grafts survived for 8 days. It implies that each “triangle” on day 7 (60% remained to survive on day 7) and day 8 (20% remained to survive on day 8) represents two grafts. Graft survival of the allogeneic control group (C57BL/6BALB/c, n=5) is equivalent to IL-6 deficiency donor graft (IL-6KOBALB/c) treated with anti-CD25 mAb (n=5) (Mantel-Cox Test, p=0.17; Gehan-Breslow-Wilcoxon Test, p=0.28), whereas IL-6 deficiency donor graft survival (IL-6KOBALB/c) treated with iso-IgG (n=5) was significantly prolonged (Mantel-Cox Test, p=0.012; Gehan-Breslow-Wilcoxon Test, p=0.0031) in comparison to allogeneic control group.</p