Search

BackgroundSepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis.Methods and designHere, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events.ConclusionThe findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis.Clinical trial registration[http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633].

BackgroundDysfunction of the immune system would disturb the intestinal homeostasis and lead to inflammatory bowel disease (IBD). Dendritic cells (DCs) help maintain intestinal homeostasis and immediately respond to pathogens or injuries once the mucosa barriers are destroyed during IBD. G protein-coupled receptors(GPR)174 is an essential regulator of immunity that is widely expressed in most immune cells, including DCs. However, the role of GPR174 in regulating the immune function of DC in colitis has not been investigated.MethodsDextran sodium sulfate (DSS) was administered to establish the mice colitis model. Data of weight, length of colon, disease activity index (DAI), and macroscopic scores were collected. The flow cytometry was used to detect the infiltrations of T cells and DCs, the mean fluorescence intensity (MFI) of CD80, CD86, CD40, and major histocompatibility complex-II (MHC-II). And T cells proliferataion was measured by carboxyfluorescein diacetate succinimidyl ester (CFSE). The expression of cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (IFN-γ), interleukin -4 (IL-4)) and GPR174 mRNA were measured by Elisa, quantitative polymerase chain reaction (qPCR), and immunofluorescence. RNA of bone-marrow-derived dendritic cells (BMDCs) was extracted for sequencing. Adoptive transfer of BMDCs was administrated intravenously.ResultsGpr174-/- mice exposed to 3% DSS showed significant alleviation characterized by reduced loss of weight, more minor colon damage, and better DAI and macroscopic scores. The expression of pro-inflammatory cytokines (TNF-α, IL-6) decreased, while anti-inflammatory cytokine (IL-10) increased compared with WT mice. In vitro, Gpr174-/- BMDCs showed less maturity, with a declined expression of MHC-II, CD80, CD86 and reduced TNF-α, higher IL-10 after LPS stimulation. Gpr174-/- BMDCs were less capable of activating OT-II naïve CD4+ T cells than WT BMDCs and induced more Th0 cells to differentiate into Treg while less into Th1. Furthermore, the transcriptome sequencing analysis exhibited that Gpr174 participated in TNF-α (NF-κB) signaling, leukocyte transendothelial migration, and Th1/Th2 cell differentiation pathways. Adoptive transfer of Gpr174-/- BMDCs to WT mice ameliorated DSS-induced colitis.ConclusionOur study indicated that GPR174 was involved in the pathogenesis of IBD by regulating the maturation of the dendritic cells to maintain immune homeostasis. TNF-α (NF-κB) signaling pathway, leukocyte transendothelial migration, and Th1/Th2 cell differentiation pathways may be the target pathway.

ObjectivesTo investigate the relationship between obesity status and perioperative outcomes in elderly patients undergoing thoracoscopic anatomic lung cancer surgery.MethodsFrom January 2016 to December 2018, we performed a monocentric retrospective cohort study among 4164 consecutive patients aged 65 years or older who underwent thoracoscopic anatomic lung cancer surgery at Shanghai Chest Hospital. Two groups were stratified by body mass index (BMI): nonobese (BMI2) and obese status (BMI≥28kg/m2). Using a 1:1 propensity score matching (PSM) analysis to compare perioperative outcomes between two groups.Results4035 older patients were eventually enrolled, with a mean age of 69.8 years (range: 65-87), and 305 patients were eligible for obese status, with a mean BMI of 29.8 ± 1.7kg/m2. Compared with nonobese patients, obese patients were more likely to have higher rates of intraoperative hypoxemia (1.2% vs 3.9%, P=0.001) and new-onset arrhythmia (2.3% vs 4.3%, P=0.034). The difference in intraoperative transfusion and conversion rates and postoperative outcomes regarding pulmonary complications, new-onset arrhythmia, transfusion, length of hospital stay, 30-day readmission and hospitalization costs between two groups were not significant (P>0.05). After a 1:1 PSM analysis, the difference in both intraoperative and postoperative complications among two groups were not significant (P>0.05). In subgroup analysis, patients with BMI≥30kg/m2 had a similar incidence of perioperative complications compared to patients with BMI between 28 and 30 kg/m2 (P>0.05).ConclusionsOur research data support evidence for “obesity paradox” and also contribute the growing body of evidence that obesity in older patients should not exclude candidates for thoracoscopic anatomic lung cancer surgery.

Nosocomial infection by multi-drug resistance Elizabethkingia spp. is an emerging concern with severe clinical consequences, particularly in immunocompromised individuals and infants. Efficient control of this infection requires quick and reliable methods to determine the appropriate drugs for treatment. In this study, a total of 31 Elizabethkingia spp., including two standard strains (ATCC 13253 and FMS-007) and 29 clinical isolates obtained from hospitals in China were subjected to single cell Raman spectroscopy analysis coupled with deuterium probing (single cell Raman-DIP). The results demonstrated that single cell Raman-DIP could determine antimicrobial susceptibility of Elizabethkingia spp. in 4 h, only one third of the time required by standard broth microdilution method. The method could be integrated into current clinical protocol for sepsis and halve the report time. The study also confirmed that minocycline and levofloxacin are the first-line antimicrobials for Elizabethkingia spp. infection.