Yuan Ying Jiang

Rivaroxaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials.

PurposeRivaroxaban is a newly developed oral medicine that direct inhibits factor Xa for the prevention and treatment of thromboembolic disorders. The objective of this study was to compare the efficacy and safety of rivaroxaban versus enoxaparin, a medicine routinely used for thromboprophylaxis after total hip or knee arthroplasty.MethodsWe performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, and Embase. The primary efficacy outcome for our meta-analysis was total venous thromboembolism (VTE) and all-cause mortality. The primary safety outcome was bleeding events, which were categorized as major, clinically relevant non-major, or minor events.ResultsEight RCTs, involving 15,586 patients, were included in our meta-analysis. Compared to enoxaparin, thromboprophylaxis with rivaroxaban was associated with significantly fewer VTE and all-cause mortality [9,244 patients, risk ratio (RR) 0.56, 95% confidence interval (CI) 0.39–0.80] cases and a similar incidence of bleeding cases (major bleeding events: 13,384 patients, RR 1.65, 95% CI 0.93-2.93; clinically relevant non-major bleeding events: 13,384 patients, RR 1.21, 95% CI 0.98–1.50; total bleeding events, 13,384 patients, RR 1.10, 95% CI 0.97–1.24). The total hip or knee arthroplasty subgroup analysis revealed consistent efficacy and safety findings.ConclusionsRivaroxaban was more effective than the recommended dose of enoxaparin and had a similar safety profile for thromboprophylaxis after hip and knee arthroplasty.

ALLICIN ENHANCES THE OXIDATIVE DAMAGE EFFECT OF AMPHOTERICIN B AGAINST CANDIDA ALBICANS

Amphotericin B (AmB) is the gold standard of antifungal treatment for the most severe invasive mycoses. In addition to the interaction of AmB with ergosterol in the fungi cell membrane, several studies have demonstrated oxidative damage involved in the fungicidal activity of AmB. In this study, allicin, an allyl sulphur compound from garlic, was shown to enhance significantly the effect of AmB against Candida albicans in vitro and in vivo, although allicin did not exert a fungicidal effect. Further study first demonstrated that allicin-mediated oxidative damage, such as phospholipid peroxidation in the plasma membrane, via influencing the defence of C. albicans against oxidative damage may be the cause of the synergistic interaction between allicin and AmB. We envision that a combination of AmB with allicin may prove to be a promising strategy for the therapy of disseminated candidiasis.

RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in Candida albicans

Abstract.The calcineurin pathway has been reported to be essential for the development of azole resistance in Candida albicans. The depletion or ectopic over-expression of RTA2 increased or decreased susceptibility of C. albicans to azoles, respectively. CaCl2- induced activation of the calcineurin pathway in wildtype C. albicans promoted resistance to azoles, while the Ca2+ chelator (EGTA), calcineurin inhibitors (FK506 and cyclosporin A) and the deletion of RTA2 blocked the resistance-promoting effects of CaCl2. Furthermore, we found that RTA2 was up-regulated in a calcineurin-dependent manner. The depletion of RTA2 also made the cell membrane of C. albicans liable to be destroyed by azoles and RTA2 over-expression attenuated the destroying effects. Finally, the disruption of RTA2 caused an increased accumulation of dihydrosphingosine (DHS), one of the two sphingolipid long-chain bases, by decreasing release of DHS. In conclusion, our findings suggest that RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans.

Moxifloxacin monotherapy versus β-lactam-based standard therapy for community-acquired pneumonia: a meta-analysis of randomised controlled trials

The aim of this study was to compare more conclusively the efficacy and safety of moxifloxacin, a new respiratory fluoroquinolone antibiotic, with beta-lactam-based standard therapy, which has been reported to possess good efficacy for community-acquired pneumonia (CAP). A meta-analysis of randomised controlled trials (RCTs) identified in PubMed, the Cochrane Library and Embase was performed. Seven RCTs, involving 3903 patients, were included in the meta-analysis. Moxifloxacin monotherapy was associated with similar clinical treatment success rates [clinically evaluable population, odds ratio (OR)=1.15, 95% confidence interval (CI) 0.81-1.64; intention-to-treat population, OR=1.11, 95% CI 0.86-1.42] and similar mortality (OR=0.98, 95% CI 0.66-1.46) compared with beta-lactam-based standard therapy for CAP. Microbiological treatment success rates in the moxifloxacin group were significantly higher than in the beta-lactam-based therapy group with a statistical margin (OR=1.69, 95% CI 1.02-2.80). No difference was found regarding the incidence of adverse events and serious adverse events between moxifloxacin and beta-lactam-based standard therapy. This meta-analysis provides evidence that moxifloxacin not only can be used as effectively and safely as beta-lactam-based standard therapy for CAP but also possesses a favourable pathogen eradication rate. The once-daily dosing of moxifloxacin monotherapy may be a useful alternative for beta-lactam-based standard therapy.

Altered protein profile of lymphocytes in an antigen-specific model of colitis: a comparative proteomic study.

Abstract.Objective:Lymphocytes are deeply involved in the initiation and perpetuation of inflammatory response in inflammatory bowel disease (IBD) and lymphocyte-derived proteins are associated with the pathogenesis of the disease. The aim of this study was to identify the altered protein profiles of lymphocytes from rats with colitis.Methods:Colitis models were induced by colonic administration of trinitrobenzene sulfonic acid (TNBS) in 50% ethanol in male SD rats. Seven days after administration of TNBS/ethanol, lymphocytes were harvested from mesenteric lymph nodes (MLNs) and proteins were extracted. Two-dimensional polyacrylamide gel electrophoresis and PDQuest 2D-image-analysis software were used to display and analyze the protein spots. The differentially-expressed proteins were identified by tryptic in-gel digestion and mass spectrometry. Real-time RT-PCR was used for selected transcripts to validate the findings of the proteomics analysis.Results:A total of 1,100 protein spots including 26 proteins with at least a two-fold difference in abundance between colitis and control groups were identified. Among all the detected spots, 17 were up-regulated and 9 were down-regulated. It was found that the altered proteins included the regulators of the cell cycle and cell proliferation, signal transduction factors, inflammatory factors, apoptosis-related proteins and metabolic enzymes.Conclusions:In lymphocytes of rats with TNBS-induced colitis, 26 altered proteins were identified. They involve inflammation, apoptosis, metabolism, and regulation of the cell cycle, cell proliferation, and signal transduction.

Dectin-1 plays an important role in host defense against systemic Candida glabrata infection

ABSTRACT Candida glabrata is the second most common pathogen of severe candidiasis in immunocompromised hosts, following C. albicans. Although C. glabrata and C. albicans belong to the same genus, they are phylogenetically distinct. C-type lectin receptors (CLRs), acting as pattern-recognition receptors (PRRs), play critical roles in host defense against C. albicans infections. However, our understanding of the specific roles of CLRs in host defense against C. glabrata is limited. Here, we explored the potential roles of the C-type lectins Dectin-1 and Dectin-2 in host defense against C. glabrata. We found that both Dectin-1-deficient mice (Dectin-1−/−) and Dectin-2-deficient mice (Dectin-2−/−) are more susceptible to C. glabrata infection. Dectin-1confers host higher sensitivity for sensing C. glabrata infections, while the effect of Dectin-2 in the host defense against C. glabrata is infection dose dependent. Dectin-1 is required for host myeloid cells recognition, killing of C. glabrata, and development of subsequent Th1 and Th17 cell-mediated adaptive immune response. Significantly impaired inflammatory responses such as inflammatory cells recruitment and cytokines release that were induced by C. glabrata were manifested in Dectin-1-deficient mice. Together, our study demonstrates that Dectin-1 plays an important role in host defense against systemic Candida glabrata infections, indicating a previous unknown control mechanism for this particular type of infection in host. Our study, therefore, provides new insights into the host defense against C. glabrata.

Ertapenem versus piperacillin/tazobactam for the treatment of complicated infections: a meta-analysis of randomized controlled trials

BackgroundErtapenem, a new carbapenem with a favorable pharmacokinetic profile, has been approved for the treatment of complicated intra-abdominal Infections (cIAIs), acute pelvic infections (APIs) and complicated skin and skin-structure infections (cSSSIs). The aim of this study is to compare the efficacy and safety of ertapenem with piperacillin/tazobactam, which has been reported to possess good efficacy for the treatment of these complicated infections.MethodsWe performed a meta-analysis of randomized controlled trials identified in PubMed, Cochrane library and Embase that compared the efficacy and safety of ertapenem with piperacillin/tazobactam for the treatment of complicated infections including cIAIs, APIs, cSSSIs. The primary efficacy outcome was clinical treatment success assessed at the test-of-cure visit. The primary safety outcome was drug related clinical and laboratory adverse events occurred during the treatment and the post-treatment period.ResultSix RCTs, involving 3161 patients, were included in our meta-analysis. Ertapenem was associated similar clinical treatment success with piperacillin/tazobactam for complicated infections treatment (clinically evaluable population, 1937 patients, odds ratios: 1.15, 95% confidence intervals: 0.89-1.49; modified intention to treat population, 2855 patients, odds ratios: 1.03, 95% confidence intervals: 0.87-1.22). All of secondary efficacy outcomes analysis obtained similar findings with clinical treatment success. No difference was found about the incidence of drug related adverse events between ertapenem and piperacillin/tazobactam groups.ConclusionThis meta-analysis provides evidence that ertapenem 1 g once a day can be used as effectively and safely as recommended dose of piperacillin/tazobactam, for the treatment of complicated infections, particularly of mild to moderate severity. It is an appealing option for the treatment of these complicated infections.

2‐Amino‐nonyl‐6‐methoxyl‐tetralin muriate activity against Candida albicans augments endogenous reactive oxygen species production – a microarray analysis study

Candida infections have become an increasingly significant problem, mainly because of the widespread nature of Candida and drug resistance. There is an urgent need to develop new classes of drugs for the treatment of opportunistic Candida infections, especially in medically complex patients. Previous studies have confirmed that 2‐amino‐nonyl‐6‐methoxyl‐tetralin muriate (10b) possesses powerful antifungal activity in vitro against Candia albicans. To clarify the underlying action mechanism, an oligonucleotide microarray study was performed in C. albicans SC5314 without and with 10b treatment. The analytical results showed that energy metabolism‐related genes, including glycolysis‐related genes (PFK1, CDC19 and HXK2), fermentation‐related genes (PDC11, ALD5 and ADH1) and respiratory electron transport chain‐related genes (CBP3, COR1 and QCR8), were downregulated significantly. Functional analysis revealed that 10b treatment increased the generation of endogenous reactive oxygen species, and decreased mitochondrial membrane potential, ubiquinone–cytochrome c reductase (complex III) activity and intracellular ATP levels in C. albicans SC5314. Also, addition of the antioxidant ascorbic acid reduced the antifungal activity of 10b significantly. These results suggest that mitochondrial aerobic respiration shift and endogenous reactive oxygen species augmentation might contribute to the antifungal activity of 10b against C. albicans. This information may prove to be useful for the development of new strategies to treat Candida infections.

Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis

Candida albicans is the most common cause of invasive fungal infections in humans. The C. albicans cell wall proteins play an important role in crucial host-fungus interactions and might be ideal vaccine targets to induce protective immune response in host. Meanwhile, protein that is specific to C. albicans is also an ideal target of vaccine. In this study, 11 proteins involving cell wall biosynthesis, yeast-to-hypha formation, or specific to C. albicans were chosen and were successfully cloned, purified and verified. The immune protection of vaccination with each recombinant protein respectively in preventing systemic candidiasis in BALB/c mice was assessed. The injection of rPmt4p vaccination significantly increased survival rate, decreased fungal burdens in the heart, liver, brain, and kidneys, and increased serum levels of both immunoglobulin G (IgG) and IgM against rPmt4p in the immunized mice. Histopathological assessment demonstrated that rPmt4p vaccination protected the tissue structure, and decreased the infiltration of inflammatory cells. Passive transfer of the rPmt4p immunized serum increased survival rate against murine systemic candidiasis and significantly reduced organ fungal burden. The immune serum enhanced mouse neutrophil killing activity by directly neutralizing rPmt4p effects in vitro. Levels of interleukin (IL)-4, IL-10, IL-12p70, IL-17A and tumor necrosis factor (TNF)-α in serum were higher in the immunized mice compared to those in the adjuvant control group. In conclusion, our results suggested that rPmt4p vaccination may be considered as a potential vaccine candidate against systemic candidiasis.