Preventing Candida albicans from subverting host plasminogen for invasive infection treatment.

Candida albicans is a common fungal pathogen in humans that colonizes the skin and mucosal surfaces of the majority healthy individuals. How C. albicans disseminates into the bloodstream and causes life-threatening systemic infections in immunocompromised patients remains unclear. Plasminogen system activation can degrade a variety of structural proteins in vivo and is involved in several homeostatic processes. Here, for the first time, we characterized that C. albicans could capture and "subvert" host plasminogen to invade host epithelial cell surface barriers through cell-wall localized Eno1 protein. We found that the "subverted" plasminogen system plays an important role in development of invasive infection caused by C. albicans in mice. Base on this finding, we discovered a mouse monoclonal antibody (mAb) 12D9 targeting C. albicans Eno1, with high affinity to the 254FYKDGKYDL262 motif in α-helices 6, ß-sheet 6 (H6S6) loop and direct blocking activity for C. albicans capture host plasminogen. mAb 12D9 could prevent C. albicans from invading human epithelial and endothelial cells, and displayed antifungal activity and synergistic effect with anidulafungin or fluconazole in proof-of-concept in vivo studies, suggesting that blocking the function of cell surface Eno1 was effective for controlling invasive infection caused by Candida spp. In summary, our study provides the evidence of C. albicans invading host by "subverting" plasminogen system, suggesting a potential novel treatment strategy for invasive fungal infections.

Da-cheng-qi decoction, a traditional Chinese herbal formula, for intestinal obstruction: systematic review and meta-analysis.

BACKGROUND: This study was aimed at determining the effects and safety of Da-Cheng-Qi decoction (DCQD) or DCQD combined with conservative therapy in patients with intestinal obstruction. MATERIALS AND METHODS: PubMed, EMBASE, Cochrane Controlled Trials Register, and several other databases were searched. Randomised controlled trials (RCTs) of DCQD or DCQD plus conservative therapy in patients with intestinal obstruction were eligible. Therapeutic effect was estimated by the improvement of clinical manifestations and diagnostic imaging; dichotomous/ordinal data assessment of overall response to therapy, adverse effects; or continuous variable were identified, including time to first bowel movement, time to first flatus, length of hospital stay. RESULTS: Sixty eligible RCTs including 6,095 patients were identified. Response rate: (1) DCQD versus conservative therapy (6 RCTs, 361 patients, RR of respond =1.13; 95% CI 0.97 to 1.31). (2) DCQD plus conservative therapy versus conservative therapy (48 RCTs, 4,916 patients, RR of respond =1.25 which favoured DCQD plus conservative therapy; 95% CI 1.20 to 1.30). Treatment effect remained similar when RCTs at high risk of bias were excluded. Time to first flatus postoperatively: (1) DCQD versus conservative therapy (2 RCTs, 240 patients, SMD=-3.65; 95% CI -8.17 to 0.87). (2) DCQD plus conservative therapy versus conservative therapy (11 RCTs, 1,040 patients, SMD=-2.09 which favoured DCQD plus conservative therapy; 95% CI -3.04 to -1.15). CONCLUSION: DCQD combined with conservative therapy may increase the success rate of conservative therapy for intestinal obstruction significantly and can shorten the duration of postoperative ileus in patients undergoing abdominal surgery compared with conservative therapy alone.

Moxifloxacin monotherapy versus beta-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.