Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits.

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO2 nanospheres with Cu2O nanoblocks. The resulting CaO2-Cu2O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO2-Cu2O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g., Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g., Prevotellaceae and Helicobacter). Our gas-driven CaO2-Cu2O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

Tissue adhesives based on chitosan for skin wound healing: Where do we stand in this era? A review.

Chitosan has been commonly used as an adhesive dressing material due to its excellent biocompatibility, degradability, and renewability. Tissue adhesives are outstanding among wound dressings because they can close the wound, absorb excess tissue exudate from the wound site, provide a moist environment, and act as a carrier for loading various bioactive molecules. They have been widely used in both preclinical and clinical treatment of skin wounds. This review summarizes recent research progresses in the application of chitosan and its derivatives for tissue adhesives. We also introduce their biomedical effects on wound adhesion, contamination isolation, antibacterial, immune regulation, and wound healing, and the strategies to achieve these functions when used as wound dressings. Finally, challenges and future perspectives of chitosan-based tissue adhesives are discussed for wound healing.

Forceps through a 14F flexible sheath for safe retrieval of a dislodged left atrial appendage occluder.

The LAmbre occluder (Lifetech Scientific, Shenzhen, China), a new device for left atrial appendage occlusion (LAAO), is increasingly used, but the retrieval procedure for dislodgements has rarely been reported in humans. We herein reported a case of safe retrieval of dislodged LAmbre occluder. The occluder dislodged to the left atrium (LA) at the end of the LAAO procedure. We failed to retrieve the device in the LA using a LASSO catheter and forceps through an 8.5F sheath. After it suddenly flowed into the aortic arch, we successfully retrieved it using the same forceps through a 14F flexible sheath. We also discuss the reasons for device dislodgment and experiences of device retrieval. We think that forceps can be used to retrieve an embolized LAmbre device in the aorta through a 14F flexible sheath.

Long non-coding RNA DANCR alleviates hypoxia-caused H9c2 cells damage through up regulation of HIF-1α.

Hypoxia is an important cause of myocardial cell loss, further inducing various heart illnesses, including acute myocardial infraction (AMI). Long non-coding RNA (LncRNA) discrimination antagonising non-protein coding RNA (DANCR) was firstly identified as epidermal cell differentiation suppressor. Here, we aimed to explore the effects and mechanism of DNACR in hypoxia-induced H9c2 cells. Hypoxic cells were made through 94% N2, 5% CO2, and 1% O2 environment for 24 h. Cell viability and apoptosis were detected via methyl thiazolyl tetrazolium (MTT) method and flow cytometry analysis, respectively. The expression of DANCR and HIF-1α was examined via qRT-PCR. The expression of proteins related to cell apoptosis and PI3K/AKT/mTOR and ERK1/2 signal pathways was examined through western blot analysis. We found that hypoxia induced obvious cell activity inhibition and apoptosis increasing in H9c2 cells. DANCR was negatively regulated under hypoxia condition. Overexpression of DANCR rescued activity and attenuated apoptosis. Moreover, the overexpression of DANCR elevated the activation of PI3K/AKT/mTOR and ERK1/2 pathways. Further study indicated that DANCR could up-regulate the expression of HIF-1α. Si-HIF-1α transfection could remove the beneficial effects of DANCR overexpression in hypoxia-caused H9c2 cells damage. In conclusion, DANCR alleviated hypoxia-caused H9c2 cells damage through positive regulation of HIF-1α.

A novel rank-based non-parametric method for longitudinal ordinal data.

Longitudinal ordinal data are common in biomedical research. Although various methods for the analysis of such data have been proposed in the past few decades, they are limited in several ways. For instance, the constraints on parameters in the proportional odds model may result in convergence problems; the rank-based aligned rank transform method imposes constraints on other parameters and the distributional assumptions with parametric model. We propose a novel rank-based non-parametric method that models the profile rather than the distribution of the data to make an effective statistical inference without the constraint conditions. We construct the test statistic of the interaction first, and then construct the test statistics of the main effects separately with or without the interaction, while "adjusted coefficient" for the case of ties is derived. A simulation study is conducted for comparison between rank-based non-parametric and rank-transformed analysis of variance. The results show that type I errors of the two methods are both maintained closer to the priori level, but the statistical power of rank-based non-parametric is greater than that of rank-transformed analysis of variance, suggesting higher efficiency of the former. We then apply rank-based non-parametric to two real studies on acne and osteoporosis, and the results also illustrate the effectiveness of rank-based non-parametric, particularly when the distribution is skewed.

[Statistical methods for comparing survival rates at a fixed time point].

Comparison of survival curves between two groups is an important part of disease prognosis study. Log-rank test is commonly used, but when the two curves' later intersecting opening is too large, the proportion of assumptions is not established, thus the Log-rank test is ineffective. We introduces five statistical tests to compare two survival curves at a fixed time points: classic method, logarithmic transformation, cloglog transformation, arcsine transformation and logit transformation. Through the study we found that if the overall survival curves are difficult to compare between groups tested with Log-rank test method or Two-stage test method, the fixed time point test can effectively determine whether there was significant difference in survival rate at a fixed time point. Among the five fixed time point tests, cloglog transformation could give more precise result.