Antifungal susceptibility profiles and drug resistance mechanisms of clinical Candida duobushaemulonii isolates from China.

Candida duobushaemulonii, type II Candida haemulonii complex, is closely related to Candida auris and capable of causing invasive and non-invasive infections in humans. Eleven strains of C. duobushaemulonii were collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), VITEK 2 Yeast Identification Card (YST), and internal transcribed spacer (ITS) sequencing. Whole genome sequencing of C. duobushaemulonii was done to determine their genotypes. Furthermore, C. duobushaemulonii strains were tested by Sensititre YeastOne™ and Clinical and Laboratory Institute (CLSI) broth microdilution panel for antifungal susceptibility. Three C. duobushaemulonii could not be identified by VITEK 2. All 11 isolates had high minimum inhibitory concentrations (MICs) to amphotericin B more than 2 µg/ml. One isolate showed a high MIC value of ≥64 µg/ml to 5-flucytosine. All isolates were wild type (WT) for triazoles and echinocandins. FUR1 variation may result in C. duobushaemulonii with high MIC to 5-flucytosine. Candida duobushaemulonii mainly infects patients with weakened immunity, and the amphotericin B resistance of these isolates might represent a challenge to clinical treatment.

Persistence of an epidemic cluster of Rhodotorula mucilaginosa in multiple geographic regions in China and the emergence of a 5-flucytosine resistant clone.

Rhodotorula mucilaginosa, an environmental yeast widely used in industry and agriculture, is also an opportunistic pathogen resistant to multi-antifungals. During the national surveillance in China, R. mucilaginosa has been documented from various hospitals and regions. At present, the molecular epidemiology of invasive infections caused by R. mucilaginosa and their resistance profiles to antifungals were unknown. Here we collected 49 strains from four hospitals located in different geographic regions from 2009 to 2019 in China, determined their genotypes using different molecular markers and quantified susceptibilities to various antifungals. Sequencing of ITS and D1/D2 regions in rDNA indicated that 73.5% (36/49) of clinical strains belong to same sequence type (rDNA type 2). Microsatellite (MT) genotyping with 15 (recently developed) tandem repeat loci identified 5 epidemic MT types, which accounted for 44.9% (22/49) of clinical strains, as well as 27 sporadic MT types. Microsatellite data indicated that the presence of an epidemic cluster including 35 strains (71.4%) repeatedly isolated in four hospitals for eight years. Single nucleotide variants (SNVs) from the whole genome sequence data also supported the clustering of these epidemic strains due to low pairwise distance. In addition, phylogenetic analysis of SNVs from these clinical strains, together with environmental and animal strains showed that the closely related epidemic cluster strains may be opportunistic, zoonotic pathogens. Also, molecular data indicated a possible clonal transmission of pan echinocandins-azoles-5-flucytosine resistant R. mucilaginosa strains in hospital H01. Our study demonstrated that R. mucilaginosa is a multi-drug resistant pathogen with the ability to cause nosocomial infection.

Antifungal Susceptibility Profiles and Resistance Mechanisms of Clinical Diutina catenulata Isolates With High MIC Values.

Diutina catenulata (Candida catenulata) is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on D. catenulata, and further research is required for its more in-depth characterization and analysis. Eleven strains of D. catenulata collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the Diutina catenulata strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in D. catenulata. All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06-0.12 µg/ml), posaconazole (0.06-0.12 µg/ml), amphotericin B (0.25-1 µg/ml), and 5-flucytosine (range, <0.06-0.12 µg/ml), whereas four isolates showed high MICs (≥4 µg/ml) for echinocandins. Strains with high MIC values for azoles showed common ERG11 mutations, namely, F126L/K143R. In addition, L139R mutations may be linked to high MICs of fluconazole. Two amino acid alterations reported to correspond to high MIC values of echinocandin, namely, F621I (F641) and S625L (S645), were found in the hot spot 1 region of FKS1. In addition, one new amino acid alteration, I1348S (I1368), was found outside of the FKS1 hot spot 2 region, and its contribution to echinocandin resistance requires future investigation. Diutina catenulata mainly infects patients with a weak immune system, and the high MIC values for various antifungals exhibited by these isolates may represent a challenge to clinical treatment.

Prevalence of nontuberculous mycobacteria in a tertiary hospital in Beijing, China, January 2013 to December 2018.

BACKGROUND: To investigate the species distribution of non-tuberculous mycobacteria (NTM) among tuberculosis (TB) specimens collected from January 2013 to December 2018 at Peking Union Medical Hospital (Beijing), China. NTM species identification was carried out by DNA microarray chip. RESULTS: Mycobacterial species were detected in 1514 specimens from 1508 patients, among which NTM accounted for 37.3% (565/1514), increasing from a proportion of 15.6% in 2013 to 46.1% in 2018 (P < 0.001). Among the 565 NTM positive specimens, the majority (55.2%) were from female patients. Furthermore, patients aged 45-65 years accounted for 49.6% of the total patients tested. Among 223 NTM positive specimens characterized further, the majority (86.2%) were from respiratory tract, whilst 3.6 and 3.1% were from lymph nodes and pus, respectively. Mycobacterium intracellulare (31.8%) and Mycobacterium chelonae / Mycobacterium abscessus (21.5%) were the most frequently detected species, followed by M. avium (13.5%), M. gordonae (11.7%), M. kansasii (7.6%), and others. CONCLUSION: The proportion of NTM among mycobacterial species detected in a tertiary hospital in Beijing, China, increased rapidly from year 2013 to 2018. Middle-aged patients are more likely to be infected with NTM, especially females. Mycobacterium intracellulare and Mycobacterium chelonae/ Mycobacterium abscessus were the most frequently detected NTM pathogens. Accurate and timely identification of NTM is important for diagnosis and treatment.

Prevalence and risk factors of ischemic stroke in rural areas of Liaoning province / 中华心血管病杂志

Objective: To explore the prevalence and risk factors of ischemic stroke in rural areas of Liaoning province. Methods: The study was a cross-sectional survey. From September 2017 to May 2018, a total of 10 926 rural residents aged ≥40 years were investigated in Chaoyang county, Lingyuan, Liaoyang county and Donggang city of Liaoning province. The investigation included questionnaire survey, physical examination and laboratory examination.Univariate and multivariate logistic regression models were used to analyze the risk factors of ischemic stroke. Results: The prevalence of ischemic stroke in the rural areas of Liaoning province was 5.51% (602/10 926), and the standardized prevalence rate was 4.04%. The standardized prevalence rate of male (5.05%) is higher than that of female (3.44%). The prevalence of ischemic stroke increased with age in both males (P<0.01) and females (P<0.01). Multivariate logistic regression analysis showed that age increase(compared with 40-49 years old group, 50-59 years old, OR=2.08, 95%CI 1.31-3.30, P=0.02; 60-69 years old, OR=3.90, 95%CI 2.51-6.05, P<0.01; 70-79 years old, OR=5.32, 95%CI 3.37-8.34, P<0.01; ≥80 years old, OR=3.64, 95%CI 2.00-6.62, P<0.01), male(OR=2.35, 95%CI 1.95-2.84, P<0.01),family history of stroke(OR=2.18, 95%CI 1.83-2.60, P<0.01),coronary heart disease (OR=2.01, 95%CI 1.52-2.66, P<0.01), hypertension (OR=2.82, 95%CI 2.21-3.60, P<0.01), diabetes mellitus (OR=1.36, 95%CI 1.11-1.67, P=0.03) and overweight/obese (OR=1.22, 95%CI 1.02-1.47, P=0.03) were the major risk factors of ischemic stroke. Conclusions: The prevalence of ischemic stroke in rural areas of Liaoning province is high. Age, male, family history of stroke, coronary heart disease, hypertension, diabetes mellitus, overweight/obesity are the risk factors of ischemic stroke in rural areas of Liaoning province.

Effect of ulipristal acetate and mifepristone at emergency contraception dose on the embryo-endometrial attachment using an in vitro human trophoblastic spheroid and endometrial cell co-culture model.

STUDY QUESTION: Do both ulipristal acetate (UPA) and mifepristone inhibit embryo-endometrial attachment at concentrations corresponding to the emergency contraception (EC) dose? SUMMARY ANSWER: Both UPA and mifepristone at concentrations corresponding to the EC dose do not have an inhibitory effect on embryo implantation, although mifepristone at a higher concentration appeared to have such an effect. WHAT IS KNOWN ALREADY: Levonorgestrel is commonly used for EC, but it only acts through inhibition of ovulation. UPA and mifepristone have higher efficacy as EC compared to levonorgestrel; while there is some suggestion that mifepristone may interfere with implantation, whether UPA has post-ovulatory action in inhibiting implantation is yet to be confirmed. STUDY DESIGN, SIZE, DURATION: An in vitro experimental study using trophoblastic spheroids made from JAr cell line as the embryo surrogate, and the Ishikawa cell line and primary human endometrial cells cultured to monolayer as the endometrial surrogate. The primary endometrial cells were collected from nine volunteer women in the mid-luteal phase with consent. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted in a university gynaecology unit. The JAr and Ishikawa cell lines (or primary endometrial cells) were treated with graded concentrations of UPA (0, 0.04, 0.4 and 4 µM) or mifepristone (0, 0.1, 1 and 10 µM) for 24 h. Embryo-endometrial attachment was studied using an in vitro JAr spheroid-endometrial co-culture model. Expressions of progesterone receptor, ß-catenin and glycogen synthase kinase 3 ß (GSK-3ß) were studied with real-time RT-PCR and Western blotting, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In the Ishikawa experiments, there was no significant difference in the JAr spheroid attachment rate after treatment with UPA at 0 (93.0%), 0.04 (93.6%), 0.4 (93.4%) and 4 (91.4%) µM concentrations (P > 0.05); the attachment rate was reduced after treatment with mifepristone only at 10 µM (79.8%, P < 0.0001) but not at 0.1 (92.1%) or 1.0 (95.2%) µM concentrations. In the primary endometrial cell experiments, again no significant difference was observed in the JAr spheroid attachment rate after treatment with UPA 4 µM (42.6%) compared to control (46.5%, P > 0.05). Both UPA and mifepristone could significantly up-regulate progesterone receptor expression. There was no significant alteration in expression of ß-catenin and GSK-3ß after treatment with UPA 4 µM or mifepristone 10 µM (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: The co-culture model is only a surrogate which may not fully represent the complicated process of embryo implantation in vivo, although there is no existing perfect model for studying implantation in vitro which fully resembles the latter. WIDER IMPLICATIONS OF THE FINDINGS: The lack of inhibitory effect on embryo implantation by UPA and possibly mifepristone at concentrations corresponding to the EC dose is an important information for contraceptive counseling. STUDY FUNDING/COMPETING INTEREST(S): We had free supply of the UPA compound used in this study from Laboratoire HRA Pharma. This work was supported by a Seed Fund from the Centre of Reproduction, Development and Growth, Faculty of Medicine, The University of Hong Kong, Hong Kong.

Influence of the Wenchuan earthquake on self-reported irregular menstrual cycles in surviving women.

OBJECTIVE: To explore the influence of stress induced by the Wenchuan earthquake on the menstrual cycles of surviving women. METHODS: Self-reports of the menstrual cycles of 473 women that survived the Wenchuan earthquake were analyzed. Menstrual regularity was defined as menses between 21 and 35 days long. The death of a child or the loss of property and social resources was verified for all surviving women. The severity of these losses was assessed and graded as high, little, and none. RESULTS: About 21% of the study participants reported that their menstrual cycles became irregular after the Wenchuan earthquake, and this percentage was significantly higher than before the earthquake (6%, p < 0.05). About 30% of the surviving women with a high degree of loss in the earthquake reported menstrual irregularity after the earthquake. Association analyses showed that some stressors of the Wenchuan earthquake were strongly associated with self-reports of menstrual irregularity, including the loss of children (RR: 1.58; 95% CI: 1.09, 2.28), large amounts of property (RR: 1.49; 95% CI: 1.03, 2.15), social resources (RR: 1.34; 95% CI: 1.00, 1.80) and the hormonal contraception use (RR: 1.62; 95% CI: 1.21, 1.83). CONCLUSIONS: Self-reported menstrual irregularity is common in women that survived the Wenchuan earthquake, especially in those who lost children, large amounts of property and social resources.

Prevalence, awareness, treatment and control of hypertension in rural adult residents of Liaoning Province / 中华心血管病杂志

<p><b>OBJECTIVE</b>The objective of this study was to estimate the current status of prevalence, awareness, treatment and control rate of hypertension in adult residents living in rural area of Liaoning Province, North China.</p><p><b>METHODS</b>The screening was finished in 2008, probability proportional to size sampling method was used to select the representative sample. Blood pressure was measured in 153481 adults (aged > 35 yr), information on history of hypertension and use of antihypertensive medications was obtained by use of a standard questionnaire.</p><p><b>RESULTS</b>Overall, hypertension prevalence rate was 41.9%, the age-specific hypertension prevalence rate was 25.0%, 37.7%, 50.2%, and 64.9% in men and 22.1%, 41.1%, 56.6% and 70.2% in women age 35 to 44 years, 45 to 54 years, 55 to 64 years, and above 65 years, respectively. Among hypertensive patients, awareness rate was only 54.1%, 39.7% patients received antihypertensive medication and blood pressure control rate (< 140/90 mm Hg) was 6.9% in all participants and was 9.3% in treated hypertensive patients.</p><p><b>CONCLUSION</b>Our results indicates that hypertension prevalence is highly while awareness, treatment and control rate of hypertension was low in rural areas of northeast China. These results underscore the urgent need to develop comprehensive strategies to improve prevention, detection, and treatment of hypertension in rural population of Liaoning province.</p>