Repolarization of Inflammation-Associated Macrophages by Dual Drug-Loaded Liposomes for Acute Lung Sepsis Antibacterial and Anti-inflammatory Therapy

Sepsis is defined as a systemic inflammatory response syndrome caused by a dysregulated host response to bacterial infection and is the leading cause of death in the intensive care unit at hospitals. At present, despite the discovery of many potential therapeutic methods for anti-infective treatment and immune-suppressing treatment, effective drug treatments for sepsis are lacking in the clinic. Herein, a coloaded dual therapeutic agent liposome (Cip·HCl/Cur@Lip-γ3) nanoplatform was developed by enveloping Cip·HCl and Cur into pH-responsive and inflammation-targeted liposomes. These liposomes simultaneously kill bacteria and regulate the polarization types of macrophages in infected lung tissue to relieve the infected microenvironment, providing antibacterial–anti-inflammatory therapy for synergetic acute lung sepsis. In vitro and in vivo results showed that Cip·HCl/Cur@Lip-γ3 exhibits excellent antibacterial properties against both Staphylococcus aureus and Pseudomonas aeruginosa and can effectively reduce inflammation and the immune response in acute lung infection. In addition, Cip·HCl/Cur@Lip-γ3 was administered to mice with acute lung infection, and the survival rate was 80% within 72 h. This study provides a nanoplatform to treat lung infection-induced sepsis, providing a strategy to design multifunctional nanomedicine for infectious disease therapy

Distribution of four SNPs in PCOS patients with hyperandrogenemia and without hyperandrogenemia.

<p>Values are mean ± SD.</p><p>^aAdjusted for age and BMI.</p><p>Distribution of four SNPs in PCOS patients with hyperandrogenemia and without hyperandrogenemia.</p

Association and stratification analysis between rs6688832 and risk of PCOS.

<p>OR, odds ratio; CI, confidence interval. Bold values indicate significant findings (<i>P</i> < 0.05).</p><p>^<b>a</b>Adjusted for age and BMI, where it was appropriate.</p><p>Association and stratification analysis between rs6688832 and risk of PCOS.</p

Clinical characteristics in PCOS women according to different genotypes of <i>H6PD</i>.

<p>Values are mean ± SD.</p><p>^a<i>P</i> values between AA and AG genotypes of rs6688832.</p><p>^b<i>P</i> values between AA and GG genotypes of rs6688832.</p><p>^c<i>P</i> values between CC and CT genotypes of rs17368528.</p><p>^d<i>P</i> values between CC and TT genotypes of rs17368528.</p><p>Clinical characteristics in PCOS women according to different genotypes of <i>H6PD</i>.</p

Genotype distribution of <i>H6PD</i> and <i>HSD11B1</i> in women with PCOS and controls.

<p>^<b>a</b>Adjusted for age and BMI.</p><p>OR, odds ratio; CI, confidence interval; Bold values indicate significant findings (<i>P</i> < 0.05).</p><p>Genotype distribution of <i>H6PD</i> and <i>HSD11B1</i> in women with PCOS and controls.</p

Table1_Prediction of necrotizing enterocolitis in very low birth weight infants by superior mesenteric artery ultrasound of postnatal day 1: A nested prospective study.docx

BackgroundNecrotizing enterocolitis (NEC) is a devastating intestinal complication that occurs mainly in very-low-birth-weight infants (VLBWI). The study's aim was to investigate the possibility of early prediction of NEC on postnatal day 1 based on superior mesenteric artery (SMA) doppler ultrasonograpy.MethodsA prospective, observational, nested case control study (ChiCTR1900026197) was conducted to enroll VLBWIs (birth weight Results370 VLBWIs were enrolled (30 NEC cases). Among the ultrasound parameters, S/D was significantly higher in the NEC group (OR: 2.081, 95% CI: 1.411–3.069, P = 0.000). The area under the receiver operating curve (AUROC) following the Logistic regression was 0.704 (95% CI: 0.566–0.842, P = 0.001). The sensitivity of S/D for predicting NEC was 52.2% and the specificity was 92.7%. The critical value of S/D was 6.944 and Youden index was 0.449. Preplanned subgroup analysis confirmed that NEC infants of different stages were characterized by different SMA bloodstream. Small for gestational age (SGA) might be a confounding factor affecting intestinal bloodflow. And infants with delayed initiation or slow advancement of feeding exhibited characteristic intestinal perfusion.ConclusionsIn VLBWI, early SMA ultrasound shows the potential to predict NEC. It is reasonable to speculate that SMA bloodstream is related to intestinal structural and functional integrity.</p

Table1_Immune Cell Landscape of Patients With Diabetic Macular Edema by Single-Cell RNA Analysis.DOCX

Purpose: We performed single-cell RNA sequencing (scRNA-seq), an unbiased and high-throughput single cell technology, to determine phenotype and function of peripheral immune cells in patients with diabetic macular edema (DME).Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from DME patients and healthy controls (HC). The single-cell samples were loaded on the Chromium platform (10x Genomics) for sequencing. R package Seurat v3 was used for data normalizing, clustering, dimensionality reduction, differential expression analysis, and visualization.Results: We constructed a single-cell RNA atlas comprising 57,650 PBMCs (24,919 HC, 32,731 DME). We divided all immune cells into five major immune cell lineages, including monocytes (MC), T cells (TC), NK cells (NK), B cells (BC), and dendritic cells (DC). Our differential expression gene (DEG) analysis showed that MC was enriched of genes participating in the cytokine pathway and inflammation activation. We further subdivided MC into five subsets: resting CD14++ MC, proinflammatory CD14++ MC, intermediate MC, resting CD16++ MC and pro-inflammatory CD16++ MC. Remarkably, we revealed that the proinflammatory CD14++ monocytes predominated in promoting inflammation, mainly by increasingly production of inflammatory cytokines (TNF, IL1B, and NFKBIA) and chemokines (CCL3, CCL3L1, CCL4L2, CXCL2, and CXCL8). Gene Ontology (GO) and pathway analysis of the DEGs demonstrated that the proinflammatory CD14++ monocytes, especially in DME patients, upregulated inflammatory pathways including tumor necrosis factor-mediated signaling pathway, I-kappaB kinase/NF-kappaB signaling, and toll-like receptor signaling pathway.Conclusion: In this study, we construct the first immune landscape of DME patients with T2D and confirmed innate immune dysregulation in peripheral blood based on an unbiased scRNA-seq approach. And these results demonstrate potential target cell population for anti-inflammation treatments.</p

Datasheet1_Prediction of necrotizing enterocolitis in very low birth weight infants by superior mesenteric artery ultrasound of postnatal day 1: A nested prospective study.docx

BackgroundNecrotizing enterocolitis (NEC) is a devastating intestinal complication that occurs mainly in very-low-birth-weight infants (VLBWI). The study's aim was to investigate the possibility of early prediction of NEC on postnatal day 1 based on superior mesenteric artery (SMA) doppler ultrasonograpy.MethodsA prospective, observational, nested case control study (ChiCTR1900026197) was conducted to enroll VLBWIs (birth weight Results370 VLBWIs were enrolled (30 NEC cases). Among the ultrasound parameters, S/D was significantly higher in the NEC group (OR: 2.081, 95% CI: 1.411–3.069, P = 0.000). The area under the receiver operating curve (AUROC) following the Logistic regression was 0.704 (95% CI: 0.566–0.842, P = 0.001). The sensitivity of S/D for predicting NEC was 52.2% and the specificity was 92.7%. The critical value of S/D was 6.944 and Youden index was 0.449. Preplanned subgroup analysis confirmed that NEC infants of different stages were characterized by different SMA bloodstream. Small for gestational age (SGA) might be a confounding factor affecting intestinal bloodflow. And infants with delayed initiation or slow advancement of feeding exhibited characteristic intestinal perfusion.ConclusionsIn VLBWI, early SMA ultrasound shows the potential to predict NEC. It is reasonable to speculate that SMA bloodstream is related to intestinal structural and functional integrity.</p

Data_Sheet_1_Oral Administration of Probiotics Reduces Chemotherapy-Induced Diarrhea and Oral Mucositis: A Systematic Review and Meta-Analysis.zip

BackgroundChemotherapy generally causes serious diarrhea and oral mucositis in cancer patients, and subsequently affects treatment. Oral administration of probiotics provides a therapeutic choice to address these limitations. This study aims to conduct a systematic review and meta-analysis on the efficacy of oral probiotic use in the management of the chemotherapy-induced adverse reactions, and to summarize the mechanisms underlying the action.MethodsWe searched PubMed, Embase, ClinicalTrials.gov, and Web of Science from the start of the study to its completion on Dec. 31, 2021. Risk of bias was assessed using Cochrane Collaboration's Tool. Statistical analysis of the acquired data was performed via the RevMan and the Stata Statistical Software. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO registration number: CRD42020220650).ResultsTwelve randomized controlled trials including 1,013 patients were recruited and analyzed via the standard procedure of meta-analysis. In contrast to the control group, orally taking probiotics significantly decreased the risk of chemotherapy-induced diarrhea (≥ 1 grade) (RR = 0.70; 95% Cl: 0.56, 0.88; P = 0.002) and oral mucositis (≥ 1 grade) (RR: 0.84; 95% Cl: 0.78, 0.91; P ConclusionsThis meta-analysis demonstrated that orally administrated probiotics has a potential to decrease chemotherapy-induced diarrhea and oral mucositis incidences. However, the efficacy of oral probiotic use against the adverse reactions needs to be further verified through more clinical trials, and the species and number of probiotics have to be optimized and standardized prior to clinical applications.Systematic Review Registrationhttps://www.crd.york.ac.uk, identifier: 220650.</p

Additional file 1 of The role of nutrition in analysis of risk factors and short-term outcomes for late-onset necrotizing enterocolitis among very preterm infants: a nationwide, multicenter study in China

Supplementary material 1