Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans.

Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

Retrospective Observational Study from a Chinese Network of the Impact of Combination Therapy versus Monotherapy on Mortality from Carbapenem-Resistant Enterobacteriaceae Bacteremia.

Data for a total of 164 bloodstream infection cases due to carbapenem-resistant Enterobacteriaceae (CRE) from 2013 to 2017 were retrospectively collected from 36 tertiary hospitals in 19 provinces in China to evaluate the outcomes and risk factors for mortality by univariable and multivariable analysis. The most frequent infecting species was Klebsiella pneumoniae (69.5%, 114/164). The overall in-hospital and 14-day mortality rates were 32.9% (54/164) and 31.1% (42/135), respectively. Multivariable analysis revealed that septic shock (adjusted odds ratio [aOR], 6.339; 95% confidence interval [CI], 1.586 to 25.332; P = 0.009), the Pitt bacteremia score (aOR, 1.300; 95% CI, 1.009 to 1.676; P = 0.042), and the Charlson comorbidity index (aOR, 1.392; 95% CI, 1.104 to 1.755; P = 0.005) were independently associated with a hazard effect on mortality. Combination therapy, especially tigecycline-based combination therapy, resulted in relatively low rates of in-hospital mortality and failure in clearance of CRE infection. Survival analysis revealed that appropriate therapy was associated with a lower 14-day mortality rate than inappropriate therapy (including nonactive therapy; P = 0.022), that combination therapy was superior to monotherapy (P = 0.036), that metallo-ß-lactamase producers were associated with a lower 14-day mortality than strains without carbapenemases or KPC-2 producers (P = 0.009), and that strains with MICs of >8 mg/liter for meropenem were associated with a higher 14-day mortality rate than those with MICs of ≤8 mg/liter (P = 0.037). Collectively, the severity of illness, meropenem MICs of >8 mg/liter, and carbapenemase-producing types were associated with the clinical outcome. Early detection of the carbapenemase type and initiation of appropriate combination therapy within 96 h might be helpful for improving survival.

The Taiji and Eight Trigrams chemistry philosophy of chiral iridium(iii) complexes with triplex stereogenic centers.

Four novel chiral iridium(iii) complexes with triplex stereogenic centers were synthesized by introducing chiral carbon atoms into cyclometalated and ancillary ligands, and separated into eight isomers, which coincide with the old Chinese philosophy Eight Trigrams. The electron circular dichroism and circularly polarized luminescence spectra of four pairs of isomers show perfect mirror images with a dissymmetry factor (glum factor) of around 0.003.

[Clinical Trials for Treatment of Stroke Patients with Dysphagia by Vitalstim Electroacupuncture Combined with Swallowing Rehabilitation Training].

OBJECTIVE: To observe the clinical effect of vitalstim electroacupuncture (EA) combined with swallowing rehabilitation training in the treatment of stroke patients with dysphagia. METHODS: A total of 80 stroke patients with dysphagia were randomized into treatment and control groups (n=40 in each group). Patients of the control group were treated by regular medication for anti-platelet aggregation and anti-coagulation, lipid-lowering, neuroprotection, blood glucose control and blood pressure control, etc. and swallowing function rehabilitation training, and those of the treatment group treated by EA stimulation of Fengchi (GB 20), Jinjin (EX-HN 12) and Yuye (EX-HN 13) with a Vitalstim Electrostimulator and manual acupuncture stimulation of Lianquan (CV 23), Tiantu (CV 22) in combination with regular medication plus swallowing function training as those mentioned in the control group. The EA and manual acupuncture stimulation treatment was conducted once daily, 6 times a week and 4 weeks altogether. The therapeutic effect was assessed by using Kubota swallowing ability test (6 levels), dysphagia subscale (0-6 scores) of the neurological deficit degrees, videofluorography (VFG) assessment (markedly effective, effective and invalid, for evaluating the function and symmetry state of the swallowing movements), and the MOS Item Short Form Health Survey (SF-36, 8 minor items of two major aspects in physiological function, mental health, emotional function, social function and overall health) for assessing the patients' daily-life quality. RESULTS: After the treatment, the dysphagia score of the treatment group was signi-ficantly lower than that of the control group (P<0.05). VFG outcomes showed that, of the two 40 patients in the control and treatment groups, 16 and 23 experienced a marked improvement, 20 and 15 were effective, 4 and 2 were ineffective, with the markedly effective rate being 40.0% and 57.5%, respectively. The daily-life quality scores for physiological function, mental health, emotional function, social function and overall health were all notably increased after the treatment in both groups, particularly in the treatment group (P<0.05). The therapeutic effects of the treatment group were remarkably superior to those of the control group in improving dysphagia (showed by dysphagia score and VFG outcomes) and life quality. CONCLUSIONS: EA treatment combined with swallowing function rehabilitation training is effective in improving swallowing ability and daily-life quality in stroke patients with dysphagia.

["Xingnao Kaiqiao" Acupuncture(Acupuncture Technique for Restoring Consciousness) Combined with Hyperbaric Oxygen in Patients with Hypoxic Ischemic Encephalopathy: Clinical Observation and Its Influence on Blood Rheology].

OBJECTIVE: To observe the effect of "Xingnao Kaiqiao" acupuncture(acupuncture technique for restoring consciousness) combined with hyperbaric oxygen in patients with hypoxic ischemic encephalopathy and assess its influence on blood rheology. METHODS: Forty patients with hypoxic ischemic encephalopathy were randomly divided into treatment group and control group with 20 cases in each group. The treatment group received "Xingnao Kaiqiao" acupuncture combined with hyperbaric oxygen, and the control group received hyperbaric oxygen only. The two groups of patients were treated once per day for 6 consecutive days, which consisted of one course of treatment, and the total treatment lasted for four courses. Before and after treatment, the patients underwent the mini mental state examination (MMSE) to evaluate cognitive function and the barthel index score for activities of daily living. The changes of whole blood viscosity, plasma viscosity, and erythrocyte aggregation index were determined. RESULTS: After treatment, both the treatment and control groups showed improvements in cognitive function，activities of daily living, and blood rheology compared with those before treatment (P<0.05). However, these improvements in the treatment group were significantly greater than those in the control group (P<0.05). CONCLUSIONS: Application of "Xingnao Kaiqiao" acupuncture combined with hyperbaric oxygen in patients with hypoxic ischemic encephalopathy can result in an integrated curative effect, a significant improvement in the blood rheology indexes, and promote the recovery of brain cells.

[Expression of proliferating cell nuclear antigen in severely damaged small intestinal mucosa due to high-dose 5-FU exposure].

OBJECTIVE: To detect the expression of proliferating cell nuclear antigen (PCNA) in severely damaged intestinal mucosa due to high-dose 5-FU exposure. METHODS: Thirty-two adult C57BL/6J mice were subjected to daily intraperitoneal high-dose 5-FU injection at 150 mg/kg for 5 consecutive days, and on days 1, 3, and 5, the mice were sacrificed to obtain the small intestinal tissue for HE straining and immunohistochemistry for detecting PCNA expression. Another 8 mice with intraperitoneal PBS injection served as the control group. RESULTS: High-dose 5-FU exposure of the mice resulted in severe intestinal mucous damage, with complete destruction of the villi and crypts and significantly increased cells positive for PCNA expression (P<0.01). CONCLUSION: High-dose 5-FU treatment can significantly increase the PCNA index, and the cells expressing PCNA can be closely associated with regeneration of the severely damaged mucosa due to the exposure.

Photochemotherapy inhibits angiogenesis and induces apoptosis of endothelial cells in vitro.

BACKGROUND: Photochemotherapy has long been used in the treatment of psoriasis; however, its mechanism has not been completely elucidated. Psoriasis is now regarded as an angiogenesis-related disease. Recent studies indicated that the inhibition of angiogenesis by photochemotherapy could be an underlying mechanism. It was found that photochemotherapy can downregulate the expression of angiogenic factors in keratinocytes. However, the direct effect of photochemotherapy on endothelial cells has not been studied. METHODS: In this study, we determined the effect of photochemotherapy on the proliferation of human microvascular endothelial cells through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and cell cycle analysis. The migration assay and in vitro tube formation assay were used to investigate the migration properties and tube formation ability of human microvascular endothelial cells after psoralen plus UVA (PUVA) treatment. The apoptosis of endothelial cells elicited by photochemotherapy was also analyzed with fluorescence-activated cell sorting analysis (FACS). RESULTS: UVA (0.8-5.0 J/cm(2)) irradiation with the presence of 8-methoxypsoralen (8-MOP) (300 ng/ml) resulted in a dose-dependent reduction in the cell viabilities of endothelial cells. FACS data showed an accumulation of cells in G0/G1 phase of cell cycle and apoptotic features of cell death after UVA irradiation with psoralen. The migration properties and tube formation ability of endothelial cells were dramatically inhibited by photochemotherapy. CONCLUSION: Our results showed that photochemotherapy inhibits angiogenesis and induces apoptosis of human microvascular endothelial cells in vitro, which may be a possible mechanism of photochemotherapy in the treatment of psoriasis.