ABSTRACT
ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.
ABSTRACT
Objective: This study investigated the efficacy and safety of a combination of lenalidomide, bortezomib, and dexametha-sone (RVD) in patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical features and responses of 48 patients with NDMM who were treated with RVD from January 2015 to May 2019 in Beijing Chaoyang Hospital were retrospectively analyzed. Results: The median age of the 48 patients was 59 years (range: 34-79). Among these, 44 patients were Durie-Salmon stageⅢ, 15 were ISS stageⅡ, 19 were ISS stageⅢ, and 12 had plasmacytoma; 32.5% of all patients were cytogenetic high-risk. All patients re-ceived a median of four cycles (range: 1-9) of the RVD regimen as induction treatment. The overall response rate was 97.9%, with 35.4% of patients achieving complete response (CR) or better. The rate of very good partial remission (VGPR) or better was increased from 64.1% (after two cycles) to 84.6% (after four cycles). The mean collection of CD34+cells was 4.2 (± 2.6)×106/kg. Negative minimal residual disease (MRD), as indicated by next-generation flow (NGF), was achieved in 20.6% of patients after induction. Two patients with positive MRD after induction became MRD negative after transplantation. Two patients developed grade 3 or 4 hematologic toxic-ity. No nonhematologic toxicity of grade 3 or 4 was observed. Conclusions: In patients with NDMM, RVD treatment resulted in signifi-cantly improved response rates and exhibited an acceptable risk-benefit profile, with no adverse impact on stem cell collection. RVD combined with transplantation significantly improved the negative rate of MRD, as indicated by NGF.
ABSTRACT
AIM:To study the dynamic alteration of low-density lipoprotein receptor ( LDLr) expression after exposure to hepatocyte growth factor (HGF) in human Tenon's capsule fibroblasts (HTFs).METHODS: HTFs were stimulated with HGF at different concentrations (0, 10, 20, 40, 80 and 160μg/L) for 12, 24, and 48 h.The viability of HTFs was analyzed by MTT assay .The expression of LDLr at mRNA and protein levels were analyzed by real-time PCR and Western blot .RESULTS:The expression of LDLr at mRNA and protein levels was positively correlated with the viability of HTFs.HGF promoted the viability of HTFs in a time-and concentration-dependent manner .At the same time , HGF pro-moted the expression of LDLr in the same manner .CONCLUSION:Exposure of HTFs to HGF induces LDLr expression at high level , suggesting that over-expression of LDLr on the HTFs may be a target receptor for controlled drug delivery , par-ticularly in anti-scarring therapy after glaucoma filtration surgery .
ABSTRACT
BACKGROUND:The outcome of cardiopulmonary resuscitation (CPR) may depend on a variety of factors related to patient status or resuscitation management. To evaluate the factors influencing the outcome of CPR after cardiac arrest (CA) will be conducive to improve the effectiveness of resuscitation. Therefore, a study was designed to assess these factors in the emergency department (ED) of a city hospital.METHODS:A CPR registry conforming to the Utstein-style template was conducted in the ED of the First Affiliated Hospital of Wenzhou Medical College from January 2005 to December 2011. The outcomes of CPR were compared in various factors groups. The primary outcomes were rated to return of spontaneous circulation (ROSC), 24-hour survival, survival to discharge and discharge with favorable neurological outcomes. Univariate analysis and multivariable logistic regression analysis were performed to evaluate factors associated with survival.RESULTS:A total of 725 patients were analyzed in the study. Of these patients, 187 (25.8％) had ROSC, 100 (13.8％) survived for 24 hours, 48 (6.6％) survived to discharge, and 23 (3.2％) survived to discharge with favorable neurologic outcomes. A logistic regression analysis demonstrated that the independent predictors of ROSC included traumatic etiology, first monitored rhythms, CPR duration, and total adrenaline dose. The independent predictors of 24-hour survival included traumatic etiology, cardiac etiology, first monitored rhythm and CPR duration. Previous status, cardiac etiology, first monitored rhythms and CPR duration were included in independent predictors of survival to discharge and neurologically favorable survival to discharge.CONCLUSIONS:Shockable rhythms, CPR duration ≤15 minutes and total adrenaline dose ≤5 mg were favorable predictors of ROSC, whereas traumatic etiology was unfavorable. Cardiac etiology, shockable rhythms and CPR duration ≤15 minutes were favorable predictors of 24-hour survival, whereas traumatic etiology was unfavorable. Cardiac etiology, shockable rhythms, CPR duration ≤15 minutes were favorable predictors of survival to discharge and neurologically favorable survival to discharge, but previous terminal illness or multiple organ failure (MOF) was unfavorable.
ABSTRACT
Objective To evaluate the feasibility of the serum galactomannan (GM) assay as a rapid detection method for the early diagnosis of invasive fungal infections (IFI) in haematological malignancy patients. Methods Thirty-nine patients with haematological malignancies at high risk of IFI were enrolled into this study. The criteria of high risk included fever (≥ 38℃) lasted for more than 96 hours, fever didn' t response to proper broad spectrum antibiotic or recurrenced after short period of response, and no antifungal drug was used in the last week. The GM assay in serum specimens were performed twice a week for 3 weeks. Thirty health donor were selected as control group to perform the serum GM assay. The sensitivity and specificity, the positive and negative predictive value (PV+, PV-) of GM assay in serum specimens were calculated and compared with traditional diagnosis methods. Results In the 39 patients, 31 patients were diagnosed as IFI by clinical evidence and the other 8 patients were diagnosed as bacteria infection. The cut-off of GM assay was 0.5. GM assay results showed that the positive rate, sensitivity, specificity, total consistent rate, PV+ and PV- were 80.6 %, 87.1%, 62.5%, 82.0%, 90.0 % and 55.6%, respectively. The Kappa rate was 0.474. In the 8 patients without IFI, 3 cases were GM positive and 2 BG positive. The time of the first positive GM assay was (2.8±4.8) d (ranged from 24 d before to 3 d after clinical diagnosis) before IFI was diagnosed. During antifungal treatment, the level of GM maintained highly in the patients with aggravation of IFI, and dropped with the IFI improving. Conclusion The results of GM assay were consistent with that of traditional IFI diagnosis. Compared with classical IFI diagnosis, the GM assay has the advantages of the early, rapid, and high sensitivity and specificity.