Isolate distribution and antifungal susceptibility of Saccharomyces cerevisiae in the national regional medical center of Southwest China for women and children during 2018-2023.

BACKGROUND: Saccharomyces cerevisiae has been considered a harmless yeast, but in recent years, increasing evidence has shown that it can cause disease in humans, especially invasive infections in infants/children and vulvovaginal infections in women. This study aimed to investigate the clinical information and antifungal susceptibility of clinical cases with S. cerevisiae and establish a foundation for the prevention and treatment of fungal infections. METHODS: This study was conducted from May 2018 to May 2023 at a national regional medical center in Southwest China for women and children. The demographic and clinical characteristics of patients isolated with S. cerevisiae were collected and analyzed. All the isolates were cultured on Sabouraud medium plates and identified by MALDI-TOF MS. The antifungal susceptibility of S. cerevisiae to 10 agents (amphotericin B, fluconazole, itraconazole, voriconazole, micafungin, caspofungin, terbinafine and 5-flucytosine) was determined via the microdilution broth method to determine the minimum inhibitory concentrations (MICs). RESULTS: A total of 75 cases of S. cerevisiae isolated from patients with vulvovaginal candidiasis (VVC, 44 cases), pneumonia (13 cases), or diarrhea (18 cases) were included after data review. The MICs of voriconazole and flucytosine for S. cerevisiae isolated from different body sites differed, with higher resistance in intestinal isolates. In this study, S. cerevisiae caused VVC, but there was no clear evidence that it was involved in pneumonia or diarrhea. Compared with those of Candida albicans, the primary pathogen of VVC, the MICs of fluconazole (11.96 ± 5.78 µg/mL vs. 67.64 ± 16.62 µg/mL, p = 0.002), itraconazole (0.77 ± 0.19 µg/mL vs. 2.31 ± 0.53 µg/mL, p = 0.008), voriconazole (0.22 ± 0.09 µg/mL vs. 5.02 ± 1.09 µg/mL, p < 0.001), and terbinafine (10.41 ± 0.84 µg/mL vs. 14.93 ± 4.77 µg/mL, p < 0.001) for S. cerevisiae (isolated from the genital tract) were significantly lower, while those of micafungin (0.14 ± 0.01 µg/mL vs. 0.06 ± 0.01 µg/mL, p < 0.001) and caspofungin (0.27 ± 0.04 µg/mL vs. 0.06 ± 0.01 µg/mL, p < 0.001) were significantly greater. CONCLUSION: Azoles remain the recommended regimen for S. cerevisiae-related VVC, and the use of amphotericin B vaginal effervescent tablets could be considered for the treatment of azole-resistant isolates. The antifungal susceptibility of S. cerevisiae varies according to the isolated source, and the pathogenicity trend of S. cerevisiae should be studied.

Antibiotic Resistance of Hemophilus influenzae Isolated from Children in Southwest China.

BACKGROUND: Hemophilus influenzae (Hi) is one of the major pediatric bacterial pneumonia pathogens that heavily threatens children's lives and global health. With widespread usage as first-line treatment, the prevalence of ß-lactam-resistant strains is increasing sharply. In order to treat Hi more effectively, a systematic study on the antibiotic resistance profiles, ß-lactamase-negative ampicillin-resistant (BLNAR) strains isolation rate, and potential BLNAR resistance mechanism in our region is needed. METHODS: This study analyzed antimicrobial susceptibility of Hi, and clinical data of Hi-infected patients retrospectively. BLNAR and ß-lactamase-positive ampicillin-clavulanate resistant strains (BLPACR) were confirmed by the Kirby-Bauer method and ß-lactamase test. ftsI gene in BLNAR was sequenced to find out whether resistance was induced by penicillin-binding protein mutation. Ampicillin susceptibility test with or without efflux pump inhibitors were done to assess efflux pump contribution in BLNAR. RT-PCR was performed to evaluate the efflux pump genes' transcription levels. RESULTS: A total of 2,561 Hi strains were isolated in our hospital from January 2016 to December 2019. Male to female ratio was 1.52:1. Median age was 10 months. Infant (< 3 years old) infection accounted for 83.72%. Hi resistance rates to sulfamethoxazole-trimethoprim, ampicillin, cefathiamidine, cefaclor, cefuroxime, cephalothin, amoxicillin-clavulanate, tetracycline, chloramphenicol, ofloxacin, cefotaxime, and rifampin were 84.28%, 78.01%, 49.80%, 41.98%, 36.58%, 33.64%, 4.55%, 4.1%, 3.37%, 1.77%, 0.99%, and 0.12%, respectively, while 1.33% were BLNAR. BLNARs were classified into four groups by mutation patterns in ftsI gene and most strains were divided to Group Ⅲ/Ⅲ-like. EmrB, ydeA and norM transcription levels in some ampicillin-resistant strains were higher than their sensitive counterparts. CONCLUSIONS: Ampicillin is not sufficiently effective as a first-line Hi infection treatment. However, ampicillin-clavulanate and cefotaxime may be a better choice. Efflux pumps, emrB, ydeA and norM play roles in the high resistance to ampicillin.

Analysis of listeriosis infection cases during pregnancy among 70 131 deliveries.

OBJECTIVE: To provide evidence for the diagnosis of listeriosis through a retrospective study of clinical features and results of pregnant women infected with listeriosis. METHODS: Twenty-nine pregnant women infected with listeriosis visiting West China Second University Hospital affiliated to Sichuan University from July 2010 to February 2019 were included in the retrospective analysis. Data like general information, clinical symptoms, laboratory results, and pathogen detection were analyzed to conclude clinical characteristics. RESULTS: The median age of 29 patients was 28 (18.0-42.0). Nine individuals visited in the second trimester, while 20 in the last trimester. The median course before visiting was 3.4 (0.1-19) days. The main symptoms of the first attendance were fever (21/29), increased white blood cells (26/29), abdominal pain (16/29), and decreased or vanished fetal movements (7/29). Samples where listeria were identified were maternal blood (14 cases), excreta from birth canal (24 cases), placenta (one case), newborn blood (seven cases), newborn sputum (eight cases), newborn excreta from auditory meatus (three cases), cerebrospinal fluid (two cases) and ocular discharge (one case). Inflammation was detected in pathological examination of placenta in all subjects. Among them, three were diagnosed with mild chorioamnionitis; five with moderate chorioamnionitis; nine with moderate-to-severe chorioamnionitis and 12 with severe chorioamnionitis. Among 33 fetuses carried by 29 subjects, fetal outcomes include six miscarriages, nine stillbirths, four newborn deaths immediately after birth and four after treatment discontinuation, nine discharges after successful treatment in hospital, and one death after treatment. As for maternal outcomes, 29 pregnant women all recovered after delivery. CONCLUSION: With the acute onset, high incidence of adverse pregnancy outcomes and low coverage of initial treatment, clinical physicians need to raise the awareness of listeriosis during pregnancy.

The first case of Ochrobactrum intermedium bacteremia in a pediatric patient with malignant tumor.

BACKGROUND: Ochrobactrum spp. are non-fermenting, Gram-negative bacilli that are regarded as emerging human pathogens of low virulence that can cause infections. The first identified case of Ochrobactrum intermedium was reported in 1998 in a liver transplantation patient with liver abcess. There are no reports of infections in pediatric patients. Here, we report the first case of O. intermedium bacteremia in a pediatric patient. CASE PRESENTATION: A two and a half years old male was admitted with fever, chills and nausea. He had been diagnosed as pineoblastoma and underwent surgical resection and chemotherapy. O. intermedium was isolated from his blood cultures and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), however, the Vitek II automated system failed to identify the organism. Then the pathogen was confirmed by 16S rDNA sequencing and average nucleotide identity result (ANI) confirmed the precise identification of O. intermedium at genomic level. In addition, the patient recovered well after antibiotic combined therapy. CONCLUSIONS: This, to our knowledge, is the first case of O. intermedium bacteremia in a pediatric patient with malignant tumor. Traditional biochemical identification methods such as API 20NE or VITEK2 system cannot differentiate O. anthropi and O. intermedium. MALDI-TOF may be a promising tool for rapid identification of microorganisms such as O. intermedium.

Effect of probiotic supplementation in pregnant women: a meta-analysis of randomised controlled trials.

Probiotics are being used increasingly in pregnant women, whereas the efficiency on pregnancy outcomes is yet lacking. PubMed, Embase and the Cochrane Library were searched. Relative risks (RR) or weighted mean differences (WMD) with 95 % CI were employed to calculate the summary outcomes. A total of eighteen randomised controlled trials (RCT) including 4356 pregnant women were eligible. The summary RR indicated that probiotic supplementation was associated with a significant decrease in the risk of atopic eczema (RR 0·68; 95 % CI 0·58, 0·81; P < 0·001) and eczema (RR 0·79; 95 % CI 0·68, 0·91; P = 0·002) without significant heterogeneity. Probiotic supplementation was associated with a prolonged gestational age (WMD 0·09; 95 % CI 0·04, 0·15; P = 0·001) with insignificant heterogeneity, whereas no significant effect was exerted on birth weight (P = 0·851). The risks of death (RR 0·34; 95 % CI 0·13, 0·91; P = 0·031) and necrotising enterocolitis (NEC) (RR 0·38; 95 % CI 0·18, 0·81; P = 0·012) were significantly reduced in pregnant women receiving probiotics without evidence of heterogeneity. These findings suggested that probiotics in pregnant women were beneficial for atopic eczema, eczema, gestational age, death and NEC.

[Preparing Bifidobacteria for Quantitative Detections].

OBJECTIVES: To compare different preparation methods for quantitative real-time PCR (qPCR) detection of Bifidobacteria. METHODS: Standard strains of Bifidobacteria were prepared with concentration gradients using strain DNA, PCR product amplification and purification, and plasmid DNA methods. The concentrations of Bifidobacteria were determined with ultraviolet spectrophotometer and real-time quantitative PCR. RESULTS: Greater than 0.99 R 2 in values of standard curves were achieved by all three preparation methods. The plasmid DNA method obtained a higher level of concentration and purity of Bifidobacteria than the other two methods ( P<0.01). CONCLUSIONS: The plasmid DNA method produces high quality preparations and is more suitable for real-time quantitative PCR, which can provide a reference for the molecular biological detection of Bifidobacteria.

Obesity in school-aged children and its correlation with gut E.coli and Bifidobacteria: a case-control study.

BACKGROUND: To determine the correlation between obesity in school-aged children and imbalance of gut microbes by examining the ratio change of intestinal Bifidobacteria and E.coli in obese children compared to non-obese controls. METHODS: A hospital-based 1:1 case-control study was performed. Fecal samples of the subjects were collected for DNA extraction and analyzed by quantitative real-time PCR (qPCR) to determine the copy number of Bifidobacteria and E.coli. The ratio of two microbes (B/E) was then calculated and statistically analyzed. RESULTS: Subjects of the obesity group and control group showed no significant difference in age, gender or height (P > 0.05); whereas they had significant differences in body weight and BMI. Copy numbers of Bifidobacteria and E.coli per gram of wet fecal samples were first determined using qPCR in both obese and normal groups, which were further used for the calculation of B/E ratio. We found that B/E ration in the two groups showed significant difference (P < 0.05). Corrected χ(2) test was performed for the two groups against B/E < 1, and it was found that there was a positive correlation (OR = 719.2, OR 95% C.I. = 81.57-6341.18) between B/E ratio decrease with childhood obesity. CONCLUSIONS: The obese children have a lower amount of Bifidobacteria and higher amount of E.coli (smaller B/E ratio) compared to normal non-obese children. It was suggested that obesity in children may be associated with the imbalance of gut microbes.

Identification of cytolytic vaginosis versus vulvovaginal candidiasis.

OBJECTIVE: This study aimed to observe the morphological characteristic of vaginal discharge in patients with cytolytic vaginosis (CV) under the microscope and to identify it in patients with CV and in patients with vulvovaginal candidiasis (VVC). METHODS: A total of 108 subjects including 21 healthy women, 33 patients with CV, and 54 patients with VVC were enrolled in the present morphological study. Vaginal discharge was collected and made into smear. The morphological characteristics of these vaginal smears with Gram staining were observed under the microscope. The smears were assessed for the quantity of lactobacilli, epithelial cell morphology, and the absence or presence of Candida species, Trichomonas vaginalis, and clue sells. RESULTS: First, the age, the level of education, and especially the status of pregnancy of patients with CV were significantly different from those of the patients with VVC. Second, the morphological characteristics of patients with CV consisted of overgrowth of lactobacilli, the presence of naked nuclei and fragments of the epithelial cells, a paucity of leukocytes, and the absence of Candida species and other pathogens. However, the morphological characteristic of patients with VVC consisted of the presence or absence of lactobacilli and the presence of normal epithelial cells, candidal spores, blastospores, hyphae, or other pathogens such as T. vaginalis and Gardnerella vaginalis. CONCLUSIONS: Both CV and VVC can be identified based on the quantity of lactobacilli, the morphology of the epithelial cells, and the absence or presence of Candida species and other pathogens, and the misdiagnosis of CV as VVC can be avoided.

[Epidemiology and Resistance Mechanisms of Group B Streptococci in Late-pregnant Maternal Birth Canal].

OBJECTIVE: To study the antibiotic-resistant rate of group B streptococci (GBS) in obstetric canal of late-pregnant women, evaluate the antibiotic-resistant status and finally to support the GBS prevention and curing by proper antibiotics. METHODS: 31 pregnant women between 35 to 37 gestational weeks were included, for whom the antibiotic sensitivity as well as the drug (erythromycin and clindamycin) resistance genes of GBS in obstetric canal was analyzed. RESULTS: 12 (38. 7%) strains of GBS were resistant to clindamycin, while 21 (67. 7%) to erythromycin, within which 12 strains were intrinsic phenotype - cMLS type-clindamycin resistance, other 9 were active efflux phenotype - MS type-clindamycin sensitive and all of which were confirmed by Double disk diffusion method. Eleven strains were mef (A) positive, and 12 strains were erm (B) positive, in which 3 with erm (C). CONCLUSIONS: In our research the GBS strains show a high erythromycin and clindamycin resistance rate. The resistance of our GBS strains are mainly caused by the ribosomal target changes induced by erm (B) and the increased efflux of clindamycin induced by mef (A).

[Clinical characteristics of children with meningitis caused by Streptococcus pneumoniae and antibiotic resistance of Streptococcus pneumoniae strains].

OBJECTIVE: To study the clinical characteristics of children with meningitis caused by Streptococcus pneumoniae (SP) and the drug sensitivity of SP strains. METHODS: A retrospective analysis was performed on the clinical data of 14 children with SP-infected meningitis between September 2008 and March 2014. RESULTS: Of the 14 cases, 8 cases (57%) aged under 2 years. 13 cases (93%) had fever, 9 cases (64%) had convulsions, and 7 cases (50%) were complicated by septicemia. Eleven cases (79%) had elevated white blood cell (WBC) counts and 10 cases (71%) had elevated serum C-reactive protein (CRP) levels. All 14 children had an elevated nucleated cell count and neutrophils were identified as the predominant cell type. CSF protein>1000 mg/dL was noted in 9 cases (64%). Ten cases (71%) were cured, 2 cases (14.2%) with sequelae and 2 cases (14.2%) died. The drug sensitivity analysis showed that SP had resistance rates of more than 60% to penicillin, erythromycin, clindamycin, tetracycline and sulfa, but it was sensitive to amoxicillin (93%), vancomycin (100%), chloramphenicol (100%) and levofloxacin (100%). CONCLUSIONS: The clinical characteristics of children with meningitis caused by SP are not different from those with meningitis caused by other bacteria. SP strains are resistant to common antibiotics used in clinical practice, so it is important to monitor the drug resistance of the strains.

Crystal Structures of the Acinetobacter baumannii Macrolide Phosphotransferase E.

Acinetobacter baumannii (A. baumannii) challenges clinical infection treatment due to its resistance to various antibiotics. Multiple resistance genes in the core genome or mobile elements contribute to multidrug resistance in A. baumannii. Macrolide phosphotransferase gene mphE has been identified in A. baumannii, which is particularly relevant to macrolide antibiotics. Here, we determined the structure of MphE protein in three states: the apo state, the complex state with erythromycin and guanosine triphosphate (GTP), and the complex state with azithromycin and guanosine. Interestingly, GTP and two magnesium ions were observed in the erythromycin-bound MphE complex. This structure captured the active state of MphE, in which the magnesium ions stabilized the active site and assisted the transfer of phosphoryl groups. Based on these structures, we verified that the conserved residues Asp29, Asp194, His199, and Asp213 play an important role in the catalytic phosphorylation of MphE leading to drug resistance. Our work helps to understand the molecular basis of drug resistance and provides reference targets for optimizing macrolide antibiotics.

Invasive Fusarium solani infection diagnosed by traditional microbial detection methods and metagenomic next-generation sequencing in a pediatric patient: a case report and literature review.

Fusarium solani, as an opportunistic pathogen, can infect individuals with immunosuppression, neutropenia, hematopoietic stem cell transplantation (HSCT), or other high-risk factors, leading to invasive or localized infections. Particularly in patients following allogeneic HSCT, Fusarium solani is more likely to cause invasive or disseminated infections. This study focuses on a pediatric patient who underwent HSCT for severe aplastic anemia. Although initial blood cultures were negative, an abnormality was detected in the 1,3-ß-D-glucan test (G test) post-transplantation. To determine the causative agent, blood samples were subjected to metagenomic next-generation sequencing (mNGS) and blood cultures simultaneously. Surprisingly, the results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and mNGS differed slightly, with mNGS identifying Nectria haematonectria, while MALDI-TOF MS based on culture showed Fusarium solani. To clarify the results, Sanger sequencing was performed for further detection, and the results were consistent with those of MALDI-TOF MS. Since the accuracy of Sanger sequencing is higher than that of mNGS, the diagnosis was revised to invasive Fusarium solani infection. With advancements in technology, various detection methods for invasive fungi have been developed in recent years, such as mNGS, which has high sensitivity. While traditional methods may be time-consuming, they are important due to their high specificity. Therefore, in clinical practice, it is essential to utilize both traditional and novel detection methods in a complementary manner to enhance the diagnosis of invasive fungal infections.

Integrating Molecular Biology and Network Pharmacology to Analyze the Antidepressant Mechanism of Glycyrrhizaglabra.

INTRODUCTION: Antidepressants have adverse effects and induce drug resistance when used excessively or frequently. Therefore, adjuvants are needed to reduce the use of antidepressants during treatment. Traditional Chinese medicine (TCM) is an important adjunctive approach to depression with safety, environmental protection, and low toxicity. Glycyrrhizaglabra (licorice, GG) is a plant commonly used in various herbal remedies. METHOD: We investigated the antidepressant activity of GG, its active constituents, and potential depression-related targets. We combined animal behavioral and molecular biological assays with network pharmacology to analyze the antidepressant mechanism of GG. GG extracts reversed lipopolysaccharide (LPS)-induced depression-like behavior in behavioral tests. We selected 56 active compounds and 695 target compounds of licorice from TCMSP. The PPI network screened 80 core targets for enrichment analysis. It shows that GG significantly affected neurodegeneration pathways, neuroactive ligand-receptor interaction, cAMP signaling pathway, serotonergic synapse, dopaminergic synapse, and MAPK signaling pathway. RESULT: Mechanistic studies showed that GG reduced IL-1ß, IL-6, and TNF-α levels, 5-HTRA1 expression, and GSK3ß phosphorylation in mouse hippocampus. It also increased BDNF and DRD1 expression and CREB and ERK1/2 phosphorylation. CONCLUSION: It shows that GG acted on these proteins to affect multiple pathways that mediate the pathogenesis of depression.

Chloramphenicol Binding Sites of Acinetobacter baumannii Chloramphenicol Acetyltransferase CatB8.

Acinetobacter baumannii is a multidrug-resistant pathogen that has become one of the most challenging pathogens in global healthcare. Several antibiotic-resistant genes, including catB8, have been identified in the A. baumannii genome. CatB8 protein, one of the chloramphenicol acetyltransferases (Cats), is encoded by the catB8 gene. Cats can convert chloramphenicol (chl) to 3-acetyl-chl, leading to bacterial resistance to chl. Here, we present the high-resolution cocrystal structure of CatB8 with chl. The structure that we resolved showed that each monomer of CatB8 binds to four chl molecules, while its homologous protein only binds to one chl molecule. One of the newly discovered chl binding site overlaps with the site of another substrate, acetyl-CoA. Through structure-based biochemical analyses, we identified key residues for chl recruiting and acetylation of chl in CatB8. Our work is of significant importance for understanding the drug resistance of A. baumannii and the effectiveness of antibiotic treatment.

Serotype, antibiotic susceptibility and whole-genome characterization of Streptococcus pneumoniae in all age groups living in Southwest China during 2018-2022.

Background: Streptococcus pneumoniae is a common pathogen that colonizes the human upper respiratory tract, causing high morbidity and mortality worldwide. This study aimed to investigate the prevalence status of S. pneumoniae isolated from patients of all ages in Southwest China, including serotype, antibiotic susceptibility and other molecular characteristics, to provide a basis for clinical antibiotic usage and vaccine development. Methods: This study was conducted from January 2018 to March 2022 at West China Hospital, West China Second University Hospital, First People's Hospital of Longquanyi District (West China Longquan Hospital), Meishan Women and Children's Hospital (Alliance Hospital of West China Second University Hospital) and Chengdu Jinjiang Hospital for Women and Children Health. Demographic and clinical characteristics of 263 pneumococcal disease (PD) all-age patients were collected and analyzed. The serotypes, sequence types (STs), and antibiotic resistance of the strains were determined by next-generation sequencing, sequence analysis and the microdilution broth method. Results: The most common pneumococcal serotypes were 19F (17.87%), 19A (11.41%), 3 (8.75%), 23F (6.46%) and 6A (5.70%). Coverage rates for PCV10, PCV13, PCV15, PCV20 and PCV24 were 36.12, 61.98, 61.98, 63.12 and 64.26%, respectively. Prevalent STs were ST271 (12.55%), ST320 (11.79%), ST90 (4.18%), ST876 (4.18%) and ST11972 (3.42%). Penicillin-resistant S. pneumoniae (PRSP) accounted for 82.35 and 1.22% of meningitis and nonmeningitis PD cases, respectively. Resistance genes msrD (32.7%), mefA (32.7%), ermB (95.8%), tetM (97.3%) and catTC (7.6%) were found among 263 isolates. Most isolates showed high resistance to erythromycin (96.96%) and tetracycline (79.85%), with more than half being resistant to SXT (58.94%). A few isolates were resistant to AMX (9.89%), CTX (11.03%), MEN (9.13%), OFX (1.14%), LVX (1.14%) and MXF (0.38%). All isolates were susceptible to vancomycin and linezolid. Conclusion: Our study provides reliable information, including the prevalence, molecular characterization and antimicrobial resistance of S. pneumoniae isolates causing pneumococcal diseases in Southwest China. The findings contribute to informed and clinical policy decisions for prevention and treatment.

[Species and drug resistance of pathogens in blood cultures from the pediatric hematology ward].

OBJECTIVE: To investigate the species and percentage changes of pathogens in blood cultures from the pediatric hematology ward, and to analyze the drug resistance of main pathogens and the risk factors for positive blood culture (sepsis). METHODS: A retrospective analysis was performed to analyze the species and drug sensitivity of the pathogens isolated from 2358 blood cultures from the pediatric hematology ward of the West China Second University Hospital between 2008 and 2011, as well as the related clinical data. RESULTS: A total of 110 strains of pathogens were isolated, with Escherichia coli (16 strains), Pseudomonas aeruginosa (12 strains) and Staphylococcus epidermidis (8 strains) being the most common ones. From 2008 to 2011, the percentage of Gram-positive bacteria decreased, while the percentage of Gram-negative bacteria increased. The detection rates of methicillin-resistant coagulase-negative Staphylococci and methicillin-resistant Staphylococcus aureus were 69% and 43% respectively, but both were sensitive to vancomycin. The detection rates of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and ESBL-producing Klebsiella pneumoniae were 69% and 62% respectively, but both were sensitive to imipenem and meropenem. Malignant tumor was a risk factor for positive blood culture (OR=3.564, P<0.05). CONCLUSIONS: A wide range of pathogens are responsible for bloodstream infection in the pediatric hematology ward and the percentages of bacteria are changing; these pathogens have a high drug resistance rate. Malignant tumor is a risk factor for positive blood culture in the pediatric hematology ward.

ΔNp63α-mediated epigenetic regulation in keratinocyte senescence.

Keratinocyte senescence contributes to skin ageing and epidermal dysfunction. According to the existing knowledge, the transcription factor ΔNp63α plays pivotal roles in differentiation and proliferation of keratinocytes. It is traditionally accepted that ΔNp63α exerts its functions via binding to promoter regions to activate or repress gene transcription. However, accumulating evidence demonstrates that ΔNp63α can bind to elements away from promoter regions of its target genes, mediating epigenetic regulation. On the other hand, several epigenetic alterations, including DNA methylation, histone modification and variation, chromatin remodelling, as well as enhancer-promoter looping, are found to be related to cell senescence. To systematically elucidate how ΔNp63α affects keratinocyte senescence via epigenetic regulation, we comprehensively compiled the literatures on the roles of ΔNp63α in keratinocyte senescence, epigenetics in cellular senescence, and the relation between ΔNp63α-mediated epigenetic regulation and keratinocyte senescence. Based on the published data, we conclude that ΔNp63α mediates epigenetic regulation via multiple mechanisms: recruiting epigenetic enzymes to modify DNA or histones, coordinating chromatin remodelling complexes (CRCs) or regulating their expression, and mediating enhancer-promoter looping. Consequently, the expression of genes related to cell cycle is modulated, and proliferation of keratinocytes and renewal of stem cells are maintained, by ΔNp63α. During skin inflammaging, the decline of ΔNp63α may lead to epigenetic dysregulation, resultantly deteriorating keratinocyte senescence.

Genomic Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolated from Neonatal Patients in Southwest China During 2017-2021.

Objective: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is spreading worldwide, becoming a serious threat to public health. The present study aimed to analyze the molecular epidemiology and drug resistance mechanism of CRKP isolated from neonatal patients in Sichuan, Southwest China. Methods: CRKP isolates were collected from neonatal patients of West China Second University Hospital from June 2017 to June 2021. Antimicrobial susceptibility testing was performed using broth microdilution. Whole-genome sequencing of all isolates were performed to determine the antimicrobial resistance genes, sequence typing, phylogenetic relationships. Results: In total, 41 nonduplicate CRKP isolates were collected. All isolates were highly resistant to the cephalosporins and carbapenems, however, they were all susceptible to amikacin, tigecycline, ciprofloxacin, and colistin. Various resistance genes were detected, blaNDM-5 (n = 35, 85.4%) was the predominant carbapenemase genes. The most common replicon type was IncX3, which was harbored by 36 (87.8%) isolates, followed by IncFIB (n = 34, 82.9%), and IncFII (n = 32, 78.0%). The 41 CRKP isolates belonged to 8 sequence types (STs) and ST789 (n = 29, all had blaNDM-5) was the dominant sequence type. Conclusion: The study revealed that blaNDM was the most dominant carbapenemase resistance gene. ST789 CRKP strains carrying blaNDM-5 were a tremendous menace to neonates in this hospital. Therefore, effectively implement prevention and control measures need to be taken for the prevention and treatment of CRKP infection in the neonatal ward.

[Clinical characteristics and pathogens of invasive fungal infections in children].

OBJECTIVE: To study the clinical characteristics and pathogens of invasive fungal infection in children. METHODS: The clinical data of 104 children who suffered from invasive fungal infections between 2008 and 2012 was retrospectively reviewed. RESULTS: Of the 104 cases, 20 occurred in neonates, 48 in infants and 36 in preschool and school-aged children (old-aged children). Prematurity (70%), hyaline membrane disease (45%) and pneumonia (30%) were commonly comorbid in the neonate group. In addition, the percentage of cases receiving total parenteral nutrition was higher in the neonate group than in the other two age groups (P<0.01). Mechanical ventilation was more frequent in neonate and infant groups than in the old-aged children (P<0.01). Hematological malignancy was the most common underlying disease, and the percentage of children who had neutropenia and accepted chemotherapy was higher in the old-aged children than in the other two age groups (P<0.05). Lung infection was the most common (61.5%), followed by sepsis (14.4%) and intestinal tract infection (12.5%), while nervous system infections were found only in old-aged children. A total of 105 strains of fungi were isolated from the 104 patients, including Candida (n=90, 85.7%), Cryptococcus (n=6) and others (n=9). The most commonly isolated species was Candida albicans (n=52, 49.5%). Non-Candida albicans Candida accounted for 36.2% (n=38). The rate of susceptibility of Candida species to 5-fluorocytosine and amphotericin B was higher than fluconazole. CONCLUSIONS: Invasive fungal infections can occur in children at various ages. There are differences in the risk factors for invasive fungal infections between age groups. Candida species are the main pathogens of childhood invasive fungal infections, and both Candida albicans and non-Candida albicans Candida are common. Fluorocytosine and amphotericin B are sensitive antifungal agents for infections caused by Candida species.