Resistance and virulence genes characteristic of a South Asia Clade (I) Candida auris strain isolated from blood in Beijing.

INTRODUCTION: Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing. METHOD: This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance. RESULTS: Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1. DISCUSSION: The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.

Severe anemia is associated with increased short-term and long-term mortality in patients hospitalized with cirrhosis.

INTRODUCTION AND OBJECTIVES: The relationship between anemia and the outcome of patients with cirrhosis is not completely clear. Therefore, we performed this large-scale epidemiological study to investigate the prevalence and severity of anemia in patients with cirrhosis and acute decompensation or liver injury and how anemia impacts short-term and long-term outcomes. PATIENTS AND METHODS: Patients with cirrhosis and acute decompensation (AD) or acute liver injury (ALI) were enrolled in the Chinese AcuTe on CHronic LIver FailurE (CATCH-LIFE) studies, which consisted of two large, multicenter, prospective, observational cohorts between January 2015 and December 2016 and July 2018 and January 2019. We conducted data analysis on the prevalence of anemia and determined the relationship between anemia and prognosis. RESULTS: Among 1979 patients, 1389 (70.2%) had anemia, among whom 599 (41.3%) had mild anemia, 595 (15.8%) had moderate anemia and 195 (2.4%) had severe anemia. A linear association between hemoglobin level and 90-day or 1-year LT-free mortality was shown, and a 10 g/L decrease in hemoglobin level was associated with a 6.8% extra risk of 90-day death and a 5.7% extra risk of 1-year death. Severe anemia was an independent risk factor for 90-day [HR=1.649 (1.100, 2.473), p=0.016] and 1-year LT-free mortality [HR=1.610 (1.159, 2.238), p=0.005]. Multinomial logistic regression analysis further identified that severe anemia was significantly associated with post-28-day mortality but not within-28-day mortality. CONCLUSIONS: Anemia is common in patients with cirrhosis admitted for acute events. Severe anemia was associated with poor 90-day and 1-year prognoses in these patients.

Hepatitis E virus superinfection impairs long-term outcome in hospitalized patients with hepatitis B virus-related decompensated liver cirrhosis.

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) superinfection is a common excerbating event in patients with chronic hepatitis B, but the impact on the long-term prognosis is not clear. This study investigates the specific role of HEV superinfection in the long-term outcome of hepatitis B virus (HBV) patients with liver cirrhosis. PATIENTS AND METHODS: A retrospective, observational cohort study was conducted using clinical, laboratory, and survival data collected from patients suffering from hepatitis B cirrhosis with or without HEV superinfection. Disease progression and mortality rates were analyzed. RESULTS: After a two-year follow-up, HEV superinfection was identified in 27 of 811 patients. The transplantation-free mortality was significantly increased (51.9% vs. 14.3%, p< 0.001) in HEV superinfection compared to that in hepatitis B cirrhosis patients without HEV superinfection. Logistic regression analysis demonstrated that elderly people were independent host risk factors for hepatitis B cirrhosis patients with HEV superinfection before and after propensity score matching (PSM). Moreover, HEV superinfection was a risk factor for patients with hepatitis B cirrhosis with new acute decompensation (AD) and acute-on-chronic liver failure (ACLF) during hospitalization. A multivariate Cox proportional hazards regression model demonstrated that acute HEV co-infection is associated with two-year mortality (hazard ratio [HR]: 2.49; 95% CI: 1.40-4.43; p= 0.002; and HR: 5.79; 95% CI: 1.87-17.87; p= 0.002) in patients with hepatitis B cirrhosis before and after PSM. CONCLUSIONS: Elder patients with hepatitis B cirrhosis are susceptible to HEV superinfection, accelerating disease progression and increasing long-term mortality in hospitalized patients with HBV-related decompensated liver cirrhosis.

A Longitudinal Study of the Effects of Bed-Sharing Experience in Infancy on Sleep Outcomes at 2 Years Old.

OBJECTIVE: To assess the effects of bed-sharing experiences in infancy on sleep patterns and sleep problems at 2 years of age. STUDY DESIGN: A total of 1564 children from an ongoing Shanghai Maternal-Child Pairs Cohort were included. Bed-sharing experiences were collected when children were 2, 6, and 24 months old via caregiver-completed questionnaires (whether caregivers shared a bed with children during the night), and children's bed-sharing experiences were classified as follows: no bed-sharing, early-only bed-sharing, late-onset bed-sharing, and persistent bed-sharing. Sleep outcomes at month 24 were assessed using the Brief Infant Sleep Questionnaire. Sleep patterns and problems were compared among the 4 types of bed-sharing experiences. RESULTS: Of the 1564 infants, 10.10% had no bed-sharing, 18.35% had early-only, 27.94% had late-onset, and 43.61% had persistent bed-sharing. Compared with children with no bed-sharing, children with late-onset and persistent bed-sharing had shorter nighttime sleep durations and longer daytime sleep durations (P < .05) and were more likely to snore (aOR 1.87 [95% CI 1.25-2.79]; aOR 1.68 [95% CI 1.14-2.47]) and have sleep onset difficulty (aOR 2.06 [95% CI 1.37-3.09]; aOR 2.07 [95% CI 1.41-3.05]). However, caregivers of infants in the late-onset and persistent bed-sharing groups perceived less problematic sleep (aOR 0.38 [95% CI 0.26-0.56] and aOR 0.40 [95% CI 0.28-0.58]). CONCLUSIONS: Bed-sharing is a common experience among Chinese children. Although bed-sharing may reduce caregivers' perception of children's problematic sleep, late-onset or persistent bed-sharing in infancy is associated with sleep problems at 2 years of age.

A modified method by differential adhesion for enrichment of bladder cancer stem cells.

PURPOSE: In a previous study the vaccine was effective against bladder cancer in a mouse model. However, a small portion of tumors regrew because the vaccine could not eliminate bladder cancer stem cells (CSCs). In this study, we showed a modified method for the isolation of bladder CSCs using a combination of differential adhesion method and serum-free culture medium (SFM) method. MATERIALS AND METHODS: Trypsin-resistant cells and trypsin-sensitive cells were isolated from MB49, EJ and 5637 cells by a combination of differential adhesion method and SFM method. The CSCs characterizations of trypsin-resistant cells were verified by the flow cytometry, the western blotting, the quantitative polymerase chain reaction, the resistance to chemotherapy assay, the transwell assay, and the tumor xenograft formation assay. RESULTS: Trypsin-resistant cells were isolated and identified in CSCs characters, with high expression of CSCs markers, higher resistance to chemotherapy, greater migration in vitro, and stronger tumorigenicity in vivo. CONCLUSION: Trypsin-resistant cells displayed specific CSCs properties. Our study showed trypsin-resistant cells were isolated successfully with a modified method using a combination of differential adhesion method and SFM method.

A modified method by differential adhesion for enrichment of bladder cancer stem cells

ABSTRACT Purpose: In a previous study the vaccine was effective against bladder cancer in a mouse model. However, a small portion of tumors regrew because the vaccine could not eliminate bladder cancer stem cells (CSCs). In this study, we showed a modified method for the isolation of bladder CSCs using a combination of differential adhesion method and serum-free culture medium (SFM) method. Materials and Methods: Trypsin-resistant cells and trypsin-sensitive cells were isolated from MB49, EJ and 5637 cells by a combination of differential adhesion method and SFM method. The CSCs characterizations of trypsin-resistant cells were verified by the flow cytometry, the western blotting, the quantitative polymerase chain reaction, the resistance to chemotherapy assay, the transwell assay, and the tumor xenograft formation assay. Results: Trypsin-resistant cells were isolated and identified in CSCs characters, with high expression of CSCs markers, higher resistance to chemotherapy, greater migration in vitro, and stronger tumorigenicity in vivo. Conclusion: Trypsin-resistant cells displayed specific CSCs properties. Our study showed trypsin-resistant cells were isolated successfully with a modified method using a combination of differential adhesion method and SFM method.