Phylogenomic analysis of the Candida auris-Candida haemuli clade and related taxa in the Metschnikowiaceae, and proposal of thirteen new genera, fifty-five new combinations and nine new species.

Candida is a polyphyletic genus of asexually reproducing yeasts in the Saccharomycotina with more than 400 species that occur in almost all families of the subclass and its name is strongly connected with the infectious disease candidiasis. During the last two decades, approximately half of the Candida species have been reassigned into more than 36 already existing genera and 14 newly proposed genera, but the polyphyletic feature of the genus largely remained. Candida auris is an important, globally emerging opportunistic pathogen that has caused life-threatening outbreaks in healthcare facilities worldwide. This species belongs to the Candida auris-Candida haemuli (CAH) clade in the Metschnikowiaceae, a clade that contains multidrug-resistant clinically relevant species, but also species isolated from natural environments. The clade is phylogenetically positioned remotely from the type species of the genus Candida that is Candida vulgaris (currently interpreted as a synonym of Candida tropicalis) and belongs to the family Debaryomycetaceae. Although previous phylogenetic and phylogenomic studies confirmed the position of C. auris in the Metschnikowiaceae, these analyses failed to resolve the position of the CAH clade within the family and its delimitation from the genera Clavispora and Metschnikowia. To resolve the position of the CAH clade, phylogenomic and comparative genomics analyses were carried out to address the phylogenetic position of C. auris and related species in the Metschnikowiaceae using several metrics, such as the average amino acid identity (AAI) values, the percentage of conserved proteins (POCP) and the presence-absence patterns of orthologs (PAPO). Based on those approaches, 13 new genera are proposed for various Candida and Hyphopichia species, including members of the CAH clade in the Metschnikowiaceae. As a result, C. auris and related species are reassigned to the genus Candidozyma. Fifty-five new combinations and nine new species are introduced and this will reduce the polyphyly of the genus Candida. Citation: Liu F, Hu Z-D, Zhao X-M, et al. 2024. Phylogenomic analysis of the Candida auris-Candida haemuli clade and related taxa in the Metschnikowiaceae, and proposal of thirteen new genera, fifty-five new combinations and nine new species. Persoonia 52: 22-43. https://doi.org/10.3767/persoonia.2024.52.02 .

Saccharomycetaceae: delineation of fungal genera based on phylogenomic analyses, genomic relatedness indices and genomics-based synapomorphies.

A correct classification of fungi, including yeasts, is of prime importance to understand fungal biodiversity and to communicate about this diversity. Fungal genera are mainly defined based on phenotypic characteristics and the results of single or multigene-based phylogenetic analyses. However, because yeasts often have less phenotypic characters, their classification experienced a strong move towards DNA-based data, from short ribosomal sequences to multigene phylogenies and more recently to phylogenomics. Here, we explore the usefulness of various genomics-based parameters to circumscribe fungal genera more correctly taking the yeast domain as an example. Therefore, we compared the results of a phylogenomic analysis, average amino acid identity (AAI) values, the presence of conserved signature indels (CSIs), the percentage of conserved proteins (POCP) and the presence-absence patterns of orthologs (PAPO). These genome-based metrics were used to investigate their usefulness in demarcating 13 hitherto relatively well accepted genera in Saccharomycetaceae, namely Eremothecium, Grigorovia, Kazachstania, Kluyveromyces, Lachancea, Nakaseomyces, Naumovozyma, Saccharomyces, Tetrapisispora, Torulaspora, Vanderwaltozyma, Zygosaccharomyces and Zygotorulaspora. As a result, most of these genera are supported by the genomics-based metrics, but the genera Kazachstania, Nakaseomyces and Tetrapisispora were shown to be genetically highly diverse based on the above listed analyses. Considering the results obtained for the presently recognized genera, a range of 80-92 % POCP values and a range of 60-70 % AAI values might be valuable thresholds to discriminate genera in Saccharomycetaceae. Furthermore, the genus-specific genes identified in the PAPO analysis and the CSIs were found to be useful as synapomorphies to characterize and define genera in Saccharomycetaceae. Our results indicate that the combined monophyly-based phylogenomic analysis together with genomic relatedness indices and synapomorphies provide promising approaches to delineating yeast genera and likely those of filamentous fungi as well. The genera Kazachstania, Nakaseomyces and Tetrapisispora are revised and we propose eight new genera and 41 new combinations. Citation: Liu F, Hu Z-D, Yurkov A, et al. 2024. Saccharomycetaceae: delinaeation of fungal genera based on phylogenomic analyses, genomic relatedness indices and genomics-based synapomorphies. Persoonia 52: 1-21. https://doi.org/10.3767/persoonia.2024.52.01.

[The clinical characteristics of 497 children with congenital pseudarthrosis of the tibia].

Objective: To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center. Methods: This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children with CPT who were treated at Department of Orthopedics, the Children's Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t-test or χ2 tests. Results: Among 497 children with CPT, there were 305 males (61.4 %) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6 %). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157);χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) (χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 cases (63.3%), followed by type Ⅱ in 100 cases (19.7%), type Ⅲ in 54 cases (10.7 %) and type Ⅰ in 32 cases (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 cases (2.8 %), in the middle third in 185 cases (36.5 %), and in the distal third in 308 cases (60.8 %). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range: 0 to 12 surgeries); 76 children (15.3 %) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases), refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times;t=14.93,P<0.01). Conclusions: Crawford type Ⅳ is the most common type of CPT in children. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Lattice distortion enabling enhanced strength and plasticity in high entropy intermetallic alloy.

Intermetallic alloys have traditionally been characterized by their inherent brittleness due to their lack of sufficient slip systems and absence of strain hardening. However, here we developed a single-phase B2 high-entropy intermetallic alloy that is both strong and plastic. Unlike conventional intermetallics, this high-entropy alloy features a highly distorted crystalline lattice with complex chemical order, leading to multiple slip systems and high flow stress. In addition, the alloy exhibits a dynamic hardening mechanism triggered by dislocation gliding that preserves its strength across a wide range of temperatures. As a result, this high-entropy intermetallic circumvents precipitous thermal softening, with extensive plastic flows even at high homologous temperatures, outperforming a variety of both body-centered cubic and B2 alloys. These findings reveal a promising direction for the development of intermetallic alloys with broad engineering applications.

A coordinated attack by a bacterial secretion system and a small molecule drives prey specificity.

Vibrio species are recognized for their role in food- and water-borne diseases in humans, fish, and aquatic invertebrates. We screened bacterial strains isolated from raw food shrimp for those that are bactericidal to Vibrio strains. Here we identify and characterize Aeromonas dhakensis strain A603 which shows robust bactericidal activity specifically towards Vibrio and related taxa but less potency toward other Gram-negative species. Using the A603 genome and genetic analysis, we show that two antibacterial mechanisms account for its vibriocidal activity -- a highly potent Type Six Secretion System (T6SS) and biosynthesis of a vibriocidal phenazine-like small molecule, named here as Ad-Phen. Further analysis indicates coregulation between Ad-Phen and a pore-forming T6SS effector TseC, which potentiates V. cholerae to killing by Ad-Phen.

[Clinicopathologic characteristics and survival analysis of primary large B-cell lymphoma of the central nervous system].

Objective: To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) . Methods: Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model. Results: Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy (P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months (P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL (HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions: In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

[Investigation of prevalence rate of osteoporosis and analysis of its influencing factors in older adults in Jiuting Town, Songjiang District, Shanghai City].

To explore the prevalence and related risk factors of osteoporosis (OP) in the elderly ≥60 years old in Jiuting Town, Songjiang District, Shanghai City. A total of 2 175 local residents aged ≥60 years old who participated in the questionnaire survey at the physical examination center of Jiuting Community Health Service Center, Songjiang District, Shanghai City from July 2021 to December 2022 were selected by a cross-sectional study with multi-stage sampling method. Questionnaire survey, blood test and bone mineral density (BMD) test were conducted.The differences in all the parameters among the elderly with different bone mass level were analyzed using t-test, chi-square test, binary logistic regression was used to screen the potential risk factors of OP.The results showed that the prevalence of OP in the elderly aged≥60 years old in Jiuting Town was 45.89%.The prevalence of OP increased gradually with the advanced age. The prevalence rate of male was significantly lower than that of female(χ2=211.94, P<0.01).Single factor analysis showed that Dairy products(χ2=9.01, P<0.05), taking calcium(χ2=42.88, P<0.05), physical exercise(χ2=24.73, P<0.05), exercise time(χ2=76.40, P<0.05) and sun exposure(χ2=55.71, P<0.05) were the protective factors for osteoporosis. Multifactor analysis showed that female(wald χ2=71.46, P<0.001) were the risk factors for osteoporosis. The age of the osteoporosis group was older than that of the non-osteoporosis group [osteoporosis group (72.47±6.89) years old, non-osteoporosis group (68.73±6.34) years old, and the difference was statistically significant, t=-11.67, P<0.05]. The waist circumference, alanine aminotransferase (ALT), creatinine (CR), blood urea nitrogen (BUN) and uric acid (UA) in the non-osteoporosis group were higher than those in the osteoporosis group, and the difference was statistically significant (all P<0.05). The levels of high-density lipoprotein (HDL)[osteoporosis group (1.34±0.35) mol/L, non-osteoporosis group (1.41±0.35) mol/L, t=-4.51, P<0.05] and alkaline phosphatase (ALP)[osteoporosis group (88.46±25.65) mol/L, osteoporosis group (94.56±32.32) mol/L, t=-4.79, P<0.05] in the osteoporosis group were lower than those in the non-osteoporosis group.Low awareness of the knowledge of osteoporosis risk factors(smoking, drinking coffee, high salt and drinking alcohol are 47.28%, 24.15%, 47.79% and 44.90%, respectively), diagnosis and treatment(The symptoms, prognosis, screening methods, medication time and follow-up screening time of osteoporosis were 26.87%, 17.88%, 21.77%, 6.65% and 15.99%, respectivel) and prevention(exercise mode, high calcium food, optimal age of calcium supplementation, the effect of vitamin D on OP, and the appropriate amount of milk to prevent osteoporosis were 33.16%, 42.01%, 13.27%, 12.07%, 9.01%, respectively) were in Jiuting Town. In conclusion, the prevalent rate of OP in the elderly ≥60 years old in Jiuting Town is 45.89%.The main risk factors are female and advanced age. Drinking tea, dairy products, combination of meat and vegetable, taking calcium, physical exercise and sun exposure were the protective factors for osteoporosis. The awareness rate of osteoporosis related knowledge is low, and health education should be strengthened in order to control and prevent the occurrence and development of osteoporosis.

[An in vitro model study of the accuracy and operation time of oral surgery robot-assisted endodontic microsurgery].

Objective: To explore the operational accuracy and operative time of oral surgery robot-assisted endodontic microsurgery on a head-simulator for clinical reference. Methods: Three pairs of surgical simulation models were set up on head-simulator. Each model included 10 positions anteriorly and posteriorly, 20 teeth for each technique, for a total of 60 teeth. An attending physician with more than 3 years clinical experience in endodontic microsurgery completed fixed-point osteotomy and apicoectomy in three groups of endodontic microsurgery under freehand (FH), static navigation (SN), and surgery robot (SR). The duration of each operation was recorded. Cone-beam CT was taken before the operation and the surgical path was planned in the software; after surgery, a plug gauge (precision gauge for measuring hole dimensions) was inserted into the surgical path for intraoral scanning. Surgical accuracy (starting point, end point, and angular deviation) was assessed in all 3 groups, and surgery time was compared. Results: The deviation at the starting point and the end point, and angular deviation was (0.37±0.11), (0.37±0.10) mm, and 0.71°±0.17°in the SR group. The deviations in the SR group were significantly lower than those in the SN group [(0.59±0.14), (0.65±0.18) mm, and 2.64°±0.75°] (P<0.05), and both groups were significantly lower than the FH group [(1.37±0.31), (1.10±0.21) mm, and 9.84°±3.15°] (P<0.05). The operative time in the SN group [(1.20±0.03) min] was significantly less than that in the SR group [(2.18±0.03) min] (P<0.05), and both groups were significantly less than that in the FH group [(8.70±3.15) min] (P<0.05). Starting point deviation, end point deviation, and angular deviation [(1.09±0.10), (0.90±0.07) mm, 7.22°±1.13°] in anterior teeth using the FH was significantly lower than the starting deviation, endpoint deviation, and angular deviation [(1.65±0.14), (1.30±0.06) mm, 12.46°±2.10°] in the posterior teeth using FH (P<0.05), and the operative time in the anterior teeth using the FH [(5.75±0.57) min] was significantly less than that in the posterior teeth using [(11.65±1.14) min] (P<0.05). The difference in accuracy and operative time between using SN and SR on anterior and posterior teeth was not statistically significant (P>0.05). Conclusions: Oral surgery robot-assisted endodontic microsurgery helps improving the accuracy of clinicians' operations and shorten the operation time.

Association of Finger Tapping Movements with Frailty Status in older Japanese Adults: A Cross-Sectional Study.

BACKGROUND: Finger tapping impairment and frailty share overlapping pathophysiology and symptoms in older adults, however, the relationship between each other has not been previously studied. OBJECTIVES: To investigate how finger tapping movements correlate with frail status in older Japanese adults. DESIGN, SETTING, AND PARTICIPANTS: Data were from a cross-sectional study called the Cognition and Activity in Rural Environment of Hokkaido Senior Survey 2018. A total of 244 community-dwelling older adults (mean age 75.3 years) were included. MEASUREMENTS: Participants underwent physical examinations, gait and finger tapping tests, and completed self-administered questionnaires. Frailty was assessed using Fried's frailty phenotype, and factor analysis was conducted to extract relevant finger tapping factors. Multinomial logistic regression was employed to analyze associations, generating adjusted odds ratios. RESULTS: Of the participants, 18 were frail, and 145 pre-frail. Analysis identified three distinct finger tapping patterns: "Range of Motion - Nondominant Hand," "Variability - Dominant Hand - Anti," and "Variability - Nondominant Hand - Anti." These patterns showed significant associations with aspects of Fried's frailty phenotype, particularly low physical activity (P = 0.002), weakness (P = 0.003), and slowness (P = 0.004). A larger range of motion in the nondominant hand correlated with a lower frailty risk (Odds Ratio: 0.09, 95% CI: 0.02-0.46), while higher variability in the same hand increased the risk of pre-frailty (Odds Ratio: 2.19, 95% CI: 1.09-4.39). CONCLUSION: Finger tapping movements are significantly associated with frailty status as determined by Fried's phenotype. The findings underscore the importance of further longitudinal studies to understand the relationship between motor function and frailty.

Predicting the response to neoadjuvant chemoradiation for rectal cancer using nomograms based on MRI tumour regression grade.

PURPOSE: This study aimed to develop nomograms that combine clinical factors and MRI tumour regression grade to predict the pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. METHODS: The retrospective study included 204 patients who underwent neoadjuvant chemoradiotherapy and surgery between January 2013 and December 2021. Based on pathological tumour regression grade, patients were categorized into four groups: complete pathological response (pCR, n=45), non-complete pathological response (non-pCR; n=159), good pathological response (pGR, n=119), and non-good pathological response (non-pGR, n=85). The patients were divided into a training set and a validation set in a 7:3 ratio. Based on the results of univariate and multivariate analyses in the training set, two nomograms were respectively constructed to predict complete and good pathological responses. Subsequently, these predictive models underwent validation in the independent validation set. The prognostic performances of the models were evaluated using the area under the curve (AUC). RESULTS: The nomogram predicting complete pathological response incorporates tumour length, post-treatment mesorectal fascia involvement, white blood cell count, and MRI tumour regression grade. It yielded an AUC of 0.787 in the training set and 0.716 in the validation set, surpassing the performance of the model relying solely on MRI tumour regression grade (AUCs of 0.649 and 0.530, respectively). Similarly, the nomogram predicting good pathological response includes the distance of the tumour's lower border from the anal verge, post-treatment mesorectal fascia involvement, platelet/lymphocyte ratio, and MRI tumour regression grade. It achieved an AUC of 0.754 in the training set and 0.719 in the validation set, outperforming the model using MRI tumour regression grade alone (AUCs of 0.629 and 0.638, respectively). CONCLUSIONS: Nomograms combining MRI tumour regression grade with clinical factors may be useful for predicting pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. The proposed models could be applied in clinical practice after validation in large samples.

[Advances in thoracic consolidation radiotherapy after first-line immunotherapy combined with chemotherapy for extensive stage small cell lung cancer].

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

Maximal diameters and mean computed tomography (CT) value of synchronous multiple pure ground-glass opacities in lung adenocarcinoma are smaller.

AIMS: Synchronous multiple pure ground-glass opacities (SMpGGOs) are observed more commonly. Nevertheless whether characteristics of SMpGGOs are similar to those of solitary pure ground-glass opacities (SpGGOs), remains unknown. This retrospective study aimed to compare radiographic characteristics between SMpGGOs and SpGGOs. MATERIALS AND METHODS: We retrospectively included patients along with SpGGOs or SMpGGOs at XXX between August 2018 and June 2020. They were enrolled in two groups (SpGGOs and SMpGGOs). The clinical records, pathologic features, and radiographic manifestations of two groups were collected and compared with SPSS 21.0. RESULTS: 138 patients (58 patients with 58 SpGGOs, 80 patients with 187 SMpGGOs) were evaluated. The threshold values of maximal diameters and mean computed tomography value for adenocarcinoma were 5.5 mm (sensitivity 86.4%, specificity 55.6%, AUC 0.777) and -615.0 Hu in SMpGGOs (sensitivity 61.4%, specificity 66.7%, AUC 0.651) for SMpGGOs, whereas 12.5 mm (sensitivity 54.5%, specificity 100%, AUC 0.851) and -531.9 Hu (sensitivity 43.2%, specificity 100%, AUC 0.724) in SpGGOs. CONCLUSION: The threshold values of maximal diameters and mean computed tomography value for adenocarcinoma in SMpGGOs may be smaller than those in SpGGOs (5.5 mm vs. 12.5mm, -615.0 Hu vs. -531.9 Hu).

Quercetin ameliorates lipid deposition in primary hepatocytes of the chicken embryo.

1. The accumulation of excessive fat plays a role in the development of non-alcoholic fatty liver disease (NAFLD) and phytogenic feed additives have the potential to ameliorate this. This study involved the isolation and culture of primary hepatocytes from chicken embryos to establish a model of hepatic steatosis induced by oleic acid/dexamethasone (OA/DEX). Lipid accumulation and cell viability were assessed using Nile Red staining, Oil Red O staining and cell count Kit -8 (CCK8) following treatment with varying concentrations of quercetin (Que). The potential mechanism by which Que exerts its effects was preliminarily investigated.2. The results indicated that OA effectively treated lipid accumulation in hepatocytes. There was no notable variance in cell proliferation between the normal and OA/DEX groups when subjected to Que treatment at concentrations of 1000 ng/ml and 10 000 ng/ml. Triglycerides and cholesterol (low and high density) decreased with Que treatment, with the most substantial reduction observed at 10 000 ng/ml.3. Gene expression levels decreased to levels similar to those in the control groups. Western blot data demonstrated that sterol regulatory element-binding protein 1 (SREBP-1) protein expression correlated with its mRNA expression level. Que mitigated lipid accumulation through the alpha serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) pathways. Expression levels of lipid-related genes (APOB, PPARα, CYP3A5 and SREBP-1) decreased to levels similar to the control groups. Western blot data demonstrated that the SREBP-1 protein expression correlated with its mRNA expression level.4. Supplementation with Que ameliorated lipid accumulation through AKT and ERK signalling pathway in OA/DEX-induced high-fat hepatocytes.

Factors influencing the therapeutic failure of high-flow nasal cannula oxygen humidification in patients with interstitial pneumonia complicated by respiratory failure.

OBJECTIVE: The aim of this study was to explore the factors influencing the treatment failure of high-flow nasal cannula (HFNC) therapy in patients with interstitial pneumonia (IP) complicated by respiratory failure. PATIENTS AND METHODS: A total of 158 patients with IP and respiratory failure treated with HFNC in our hospital from January 2020 to August 2023 were selected as the study population. Based on treatment efficacy, they were categorized into the HFNC treatment failure group and the HFNC treatment success group. Clinical data were compared between the two groups. Multiple logistic regression analysis was employed to identify independent factors influencing treatment failure, and the predictive value of these factors for HFNC treatment failure was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: After 7 days of HFNC treatment, among the 158 patients with IP and respiratory failure, 25 (15.8%) declared treatment failure, while the remaining 133 (84.2%) showed treatment success. Patients in the HFNC treatment failure group had significantly higher age, duration of IP, pre-treatment respiratory rate, C-reactive protein (CRP), and controlling nutritional status (CONUT) scores compared to the HFNC treatment success group. The PaO2/FiO2 ratio, left ventricular ejection fraction, and Glasgow Coma Scale (GCS) were significantly lower in the HFNC treatment failure group (p<0.05). Multiple logistic regression analysis revealed that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores were independent factors influencing HFNC treatment failure in patients with IP and respiratory failure (p<0.05). Lower PaO2/FiO2 ratio and GCS scores, and higher CRP and CONUT scores were associated with an increased risk of HFNC treatment failure. ROC curve analysis indicated that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores in patients with IP and respiratory failure had a high predictive value for HFNC treatment failure (p<0.05). CONCLUSIONS: The HFNC failure rate in patients with IP and respiratory failure is 15.8%. Pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores are independent factors associated with HFNC treatment failure and warrant clinical attention.

Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis.

Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis.