Nanopore sequencing of infectious fluid is a promising supplement for gold-standard culture in real-world clinical scenario.

Introduction: Infectious diseases are major causes of morbidity and mortality worldwide, necessitating the rapid identification and accurate diagnosis of pathogens. While unbiased metagenomic next-generation sequencing (mNGS) has been extensively utilized in clinical pathogen identification and scientific microbiome detection, there is limited research about the application of nanopore platform-based mNGS in the diagnostic performance of various infectious fluid samples. Methods: In this study, we collected 297 suspected infectious fluids from 10 clinical centers and detected them with conventional microbiology culture and nanopore platform-based mNGS. The objective was to assess detective and diagnostic performance of nanopore-sequencing technology (NST) in real-world scenarios. Results: Combined with gold-standard culture and clinical adjudication, nanopore sequencing demonstrated nearly 100% positive predictive agreements in microbial-colonized sites, such as the respiratory and urinary tracts. For samples collected from initially sterile body sites, the detected microorganisms were highly suspected pathogens, and the negative predictive agreements were relatively higher than those in the microbial-colonized sites, particularly with 100% in abscess and 95.7% in cerebrospinal fluid. Furthermore, consistent performance was also observed in the identification of antimicrobial resistance genes and drug susceptibility testing of pathogenic strains of Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii. Discussion: Rapid NST is a promising clinical tool to supplement gold-standard culture, and it has the potential improve patient prognosis and facilitate clinical treatment of infectious diseases.

Roles of small-dose recombinant human brain natriuretic peptide without bolus in Chinese older patients with septic cardiac dysfunction.

PURPOSE: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As one of the most common organs is affected by sepsis, cardiac dysfunction increases adverse prognosis. This study was designed to analyze the roles of small-dose recombinant human brain natriuretic peptide without bolus in Chinese older patients with septic cardiac dysfunction. METHODS: This study recruited 250 Chinese older patients with sepsis cardiac dysfunction in intensive care unit. Participants were randomly allocated into the control group (n = 125) and recombinant human brain natriuretic peptide group (n = 125). The control group received early goal-directed therapy, and the recombinant human brain natriuretic peptide group received recombinant human brain natriuretic peptide therapy in addition to early goal-directed therapy. RESULTS: There was no significant difference in medical histories, infection types, failing organs, mortality within 28 days [37 (29.6%) vs. 34 (27.2%)], intensive care unit stay [27 (21.6) vs. 22 (17.6)] and hospital stay [41 (32.8%) vs. 37 (29.6%)] between the control and recombinant human brain natriuretic peptide groups (P > 0.05 for all). Lengths of intensive care unit [16 (13-22) days] and hospital stay [25 (22-30) days] in the recombinant human brain natriuretic peptide group were significantly shorter than in the control group [21 (14-23) days; 27 (23-30) days; P < 0.05 for all]. There was no significant difference in mean daily Sequential Organ Failure Assessment score between the two groups (P > 0.05 for all). Cardiovascular and respiratory scores (P < 0.05 for all) but not other organ scores (P > 0.05 for all) were significantly lower in the recombinant human brain natriuretic peptide group than in the control group. CONCLUSIONS: Small-dose recombinant human brain natriuretic peptide was unable to lower the mortality and improve the liver, renal, and coagulation functions, but able to shorten the length of hospital stay and improve the cardiovascular and respiratory functions in Chinese older patients with septic cardiac dysfunction.

Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection.

Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality. Therapeutic interventions are lacking and disease pathogenesis is yet to be fully elucidated. The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood. Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity. The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching. Expansion and impairment of antibody secretion is a signature of fatal SFTSV infection. Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.

18F-FDG PET/CT may be a suitable method for preoperative diagnosis and evaluation of Chinese older patients with hilar cholangiocarcinoma.

BACKGROUND: As the most common cholangiocarcinoma, hilar cholangiocarcinoma (HCCA) is a challenge in hepatobiliary surgery and causes a very poor prognosis. This study was designed to explore whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) may be a suitable method for preoperative diagnosis and evaluation of Chinese older patients with hilar cholangiocarcinoma. METHODS: This study enrolled 53 patients (≥ 65 years) with HCCA. 18F-FDG PET/CT scan was performed in all patients within one week before operation. RESULTS: 18F-FDG PET/CT identified the tumors in all patients (100%). There were 48 patients (90.6%) with the same Bismuth-Corlette classifications determined by 18F-FDG PET/CT and operative pathology, whereas Bismuth-Corlette classifications of 5 patients (9.4%) were underestimated by 18F-FDG PET/CT compared with that determined by operative pathology. 18F-FDG PET/CT identified 19 patients (sensitivity: 67.9%) in 28 patients with lymph node metastases, and 22 patients (specificity: 88.0%) in 25 patients without lymph node metastases, with an accuracy of 77.4%. 18F-FDG PET/CT identified 8 patients (sensitivity: 47.1%) in 17 patients with liver, peritoneal or other distant metastases, and 35 patients (specificity: 97.2%) in 36 patients without liver, peritoneal or other distant metastases, with an accuracy of 81.1%. 18F-FDG PET/CT identified 17 patients (sensitivity: 73.9%) in 23 patients with unresectable tumors, and 24 patients (specificity: 80.0%) in 30 patients with resectable tumors, with an accuracy of 77.4%. CONCLUSIONS: 18F-FDG PET/CT may be a suitable method for preoperative diagnosis and evaluation, and offer valuable information for effective operation in Chinese older patients with HCCA.

Monoclinic Lu2-xSmxWO6-Based White Light-Emitting Phosphors: From Ground-Excited-States Calculation Prediction to Experiment Realization.

Through ground state and constrained density function calculations, Sm3+ ions luminescence in self-activated monoclinic Lu2WO6 was originated from intra 4f → 4f transitions, not inter 5d → 4f transitions. Theoretically the white luminescence was obtained by combining red and blue-green emissions of 4f energy levels and W-O charge transfer transitions. Experimentally, pure and Sm3+ doping Lu2WO6 powders were synthesized using solid phase reaction calcined in air atmosphere. By the analysis of X-ray photoelectron spectroscopy and Rietveld refinement, element Sm charge state was trivalent, and Sm3+ doping was concentration-dependent selectively doping in three Lu sites. With the increase of Sm3+ concentrations, the color coordinates changed gradually from blue (0.17, 0.17) through white light (0.33, 0.25) toward orange (0.44, 0.32) in the visible spectral under 325 nm excitation. On the basis of the theoretical prediction and experimental preparation, a white emission LED lamp was produced using a 365 nm ultraviolet chip and Lu1.99Sm0.01WO6 phosphor. The present design method can be applied to select excellent activators from a large number of rare-earth (Re) ions like Sm3+ and Eu3+/2+ or non-Re ions like Bi3+ and Mn4+ in various matrixes.

Downregulation of Interferon-ß and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease with high mortality and increasing prevalence in the East Asia. Though the etiological agent has been identified as a novel Bunyavirus, cellular mechanisms of viral pathogenesis and host immune response to SFTS virus infection remain unknown. A comprehensive study was conducted on a cohort of 70 patients on clinical manifestations, viral loads, modulation of cytokines, serum interferon level, immune related gene expression in peripheral blood cells, and dynamic changes of circulating dendritic cells during the acute phase of SFTSV infection. We found that high level viremia, reduced platelets, coagulation dysfunction, multi-organ injuries, elevated IL-6 and TNF-α were closely associated with the aggravation of SFTS. In addition, we demonstrated strong correlations between disease severity and the decline of serum IFN-ß and IL-1ß level, reduction of myeloid dendritic cells (mDCs) and suppressed Toll like receptor 3 expression in monocytes and mDCs. In general, dysfunction of innate immune response and cytokine storm are both involved in the pathogenesis of SFTS. Reduction of myeloid DCs contributes to the fatal outcome of SFTS virus infection, and the regulation of TLR3 could probably be the mechanism.

Regulation of p53 level by UBE4B in breast cancer.

p53 is possibly the most important mammalian tumor suppressor and it is mutated or lost in more than half of all human cancers. The stability of p53 is primarily determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. UBE4B has been shown to physically interact with p53 and Hdm2 and to negatively regulate p53 stability and function. However, no one has determined whether UBE4B promotes p53 degradation in breast cancer. In this study, UBE4B promoted the degradation and ubiquitination of p53 to inhibit the apoptosis of cancer cells and promote tumorigenesis. Our results indicate that UBE4B regulates p53 in breast cancer and could be a viable target for developing new therapeutic strategies for breast cancer treatment.