A robust web-based tool to predict viral shedding in patients with Omicron SARS-CoV-2 variants.

Background: Data on viral kinetics and variants affecting the duration of viral shedding were limited. Our objective was to determine viral shedding in distinct severe acute respiratory syndrome coronavirus 2 variants, including Omicron BA.4/5 and BF.7, and to identify the relevant influencing factors. Methods: We carried out a longitudinal cohort study at Beijing Xiaotangshan Fangcang shelter hospital from May to June 2022 (Omicron BA.4/5) and from November to December 2022 (Omicron BF.7). Nucleocapsid protein (N) and open reading frame (ORF) genes were considered as the target genes of the reverse transcription PCR. The daily results of cycle threshold (CT), including lowest ORF1ab-CT values for days 1-3 post-hospitalisation and lowest N-CT values for days 1-3 post-hospitalisation (CT3minN) and demographic and clinical characteristics were collected. Results: 1433 patients with coronavirus disease 2019 (COVID-19) were recruited from the Fangcang shelter hospital, in which 278 patients were diagnosed with Omicron BA.4/5 and 1155 patients with Omicron BF.7. Patients with BF.7 infection showed a longer duration of viral shedding. The duration of viral shedding was associated with the variants age, alcohol use, the severity of COVID-19 and CT3minN. Moreover, the nomogram had excellent accuracy in predicting viral shedding. Conclusions: Our results indicated that patients with Omicron BF.7 had a longer period of contagiousness than those with BA.4/5. The duration of viral shedding was affected by a variety of factors and the nomogram may become an applicable clinical instrument to predict viral shedding. Furthermore, we developed a new COVID-19 viral shedding predicting model that can accurately predict the duration of viral shedding for COVID-19, and created a user-friendly website to apply this prediction model (https://puh3.shinyapps.io/CVSP_Model/).

Impact of Lianhua Qingwen on viral shedding in omicron mild/asymtomatic patients: a real-world study.

Background: Lianhuaqingwen (LHQW), a traditional Chinese medicine comprised of 13 herbal extracts renowned for their robust heat-clearing and detoxifying properties, has gained widespread utilization in China but has yet to garner similar recognition abroad. It is believed to exhibit efficacy in ameliorating symptoms in individuals afflicted with coronavirus disease 2019 (COVID-19). However, the precise impact of LHQW on viral shedding (VS), particularly in the context of mild or asymptomatic infections caused by the Omicron BF.4/5 or BF.7 variants of COVID-19, remained inadequately elucidated. Consequently, a real-world study was conducted, involving patients diagnosed with COVID-19, with the primary objective of ascertaining the effectiveness of LHQW in this specific clinical context. Methods: We conducted an investigation on Omicron-infected patients through a single-center, propensity score-matched real-world study conducted at Xiaotangshan Fangcang Hospital from May to November 2022. A total of 3,368 COVID-19 patients were enrolled in the study, all of whom presented mild or asymptomatic infections caused by either BF.4/5 or BF.7 strains of the virus. Demographic and clinical data were systematically collected from medical records. Patients were allocated to receive treatment with LHQW (designated as the treatment group) or received no LHQW treatment (designated as the not-treated/no-treatment group). Viral load was quantified utilizing quantitative real-time PCR (qPCR), and the duration of VS was defined as the time interval between the initial negative test result and the date of COVID-19 diagnosis or symptom onset. Results: The study encompassed a cohort of 3,368 patients, and following propensity score matching, a subset of 296 patients was meticulously chosen for subsequent analysis. Notably, baseline characteristics exhibited disparities between the treatment and not-treated/no-treatment groups. However, post-matching, these characteristics achieved a commendable level of comparability. Our findings unequivocally demonstrated that there existed no statistically significant disparity in VS. This holds true when comparing patients subjected to LHQW treatment against those not administered LHQW, as well as when contrasting individuals presenting asymptomatic and mild COVID-19 manifestations. Conclusion: No statistically significant difference in VS was observed between patients who underwent LHQW treatment and those who did not. Additional investigations are imperative to provide a comprehensive assessment of LHQW's efficacy, particularly in patients afflicted with severe COVID-19 or those infected with viral strains distinct from BF.4/5 or BF.7.

Presepsin as a prognostic biomarker in COVID-19 patients: combining clinical scoring systems and laboratory inflammatory markers for outcome prediction.

BACKGROUND: There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking. METHODS: A total of 226 COVID-19 patients admitted to Beijing Youan Hospital's emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed. RESULTS: A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p < 0.001). Presepsin showed significant predictive value for 28-day mortality in COVID-19 patients, with an area under the ROC curve of 0.828 (95% CI: 0.737-0.920). Clinical scoring systems and inflammation markers also played a significant role in predicting 28-day outcomes. After Cox regression adjustment, Presepsin, qSOFA, NEWS2, PSI, CURB-65, CRP, NLR, CAR, and LCR were identified as independent predictors of 28-day mortality in COVID-19 patients (all p-values < 0.05). Combining Presepsin with clinical scoring systems and inflammation markers further enhanced the predictive value for patient prognosis. CONCLUSION: Presepsin is a favorable indicator for the prognosis of COVID-19 patients, and its combination with clinical scoring systems and inflammation markers improved prognostic assessment.

Mitochondrial Metabolism in Alveolar Macrophages of Patients Infected with HIV, Tuberculosis, and HIV/Tuberculosis.

Tuberculosis (TB) is one of the most common opportunistic infections and is a leading cause of mortality in patients with HIV and AIDS. HIV infection causes serious defects in the host immune system and increases the risk of active TB. TB infection promotes HIV replication and aggravates host damage in patients with HIV/AIDS. Alveolar macrophages (AMs) are essential immune cells during TB and HIV infections. AMs undergo a shift in mitochondrial metabolism during TB or HIV infection, that is, metabolic reprogramming, allowing them to act in the form of classical activated macrophages (M1) and alternative activated macrophages (M2) at different stages of infection. We reviewed the alterations in the mitochondrial energy metabolism of AMs in patients with HIV, TB, and HIV/TB to provide ideas for further research on the role of metabolic reprogramming by AMs in the pathogeneses of HIV, TB, and HIV/TB coinfection.

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

During the Omicron Pandemic Wave, the Severe Systemic Inflammatory Status of COVID-19 Indicated a Higher Risk of In-Hospital Mortality and Mediated the Clinical Efficacy of Corticosteroids.

Background: For the distinct immune/inflammatory responses from Omicron variant infection, this study aimed to investigate the diagnostic efficacy of systemic inflammatory indicators and the clinical efficacy of corticosteroids on the in-hospital mortality among COVID-19 patients. Methods: Under a retrospective cohort study, 1081 COVID-19 patients were recruited from Beijing Youan Hospital, Capital Medical University between November 16, 2022 and January 30, 2023. We chose neutrophil-to-lymphocyte ratio (NLR), CRP-to-lymphocyte ratio (CLR), and CRP-to-albumin ratio (CAR) as the systemic inflammatory indicators. Receiver operating curve (ROC) and multivariate logistic regression analysis were used to determine the diagnostic efficacy of systemic inflammatory indicators and the association between systemic inflammatory indicators and in-hospital mortality. Results: Among 684 patients included in analysis, 96 died during hospitalization. NLR, CLR and CAR performed well (with an area under the curve (AUC) greater than 0.75) in discriminating in-hospital mortality among COVID-19 patients. The severe status of systemic inflammation, with optimal cut-off value derived from ROC analysis, significantly associated higher risk of in-hospital mortality (OR = 3.81 for NLR ≥ 6.131; OR = 3.76 for CLR ≥ 45.455; OR = 5.10 for CAR ≥ 1.436). Corticosteroids use within 72 hours of admission increased the in-hospital mortality 2.88-fold for COVID-19 patients. In the subgroup of patients with severe systemic inflammation, corticosteroids increased the risk of in-hospital mortality (OR = 2.11 for NLR, p = 0.055; OR = 2.94 for CLR, p = 0.005; OR = 2.31 for CAR, p = 0.036). Conclusion: Systemic inflammatory indicators had good diagnostic performance for in-hospital mortality. Patients with severe systemic inflammatory status should not receive corticosteroid treatment and further studies are warranted for confirmation.

Comparative analysis of monocyte-derived dendritic cell phenotype and T cell stimulatory function in patients with acute-on-chronic liver failure with different clinical parameters.

Background: Acute-on-Chronic Liver Failure (ACLF) patients experience systemic inflammation as well as immune dysfunction and exhaustion. The phenotype and functionality of monocyte-derived dendritic cells in ACLF patients with different clinical parameters have not been elucidated. Methods: This study included 37 cases of ACLF, 20 cases of Chronic Hepatitis B (CHB) patients, and 12 healthy controls. Demographic and laboratory parameters were collected from the enrolled patients. Peripheral blood samples were obtained from the participants. Monocyte-derived dendritic cells were induced and cultured, followed by co-culturing with T cells from the patients. Cell surface markers and intracellular markers were analyzed using flow cytometry. The relationship between these markers and clinical parameters was compared. Results: Our study found that ACLF patients had lower expression levels of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells compared to both CHB patients and healthy controls. IL-4, GM-CSF, and alcohol were found to promote the expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. In ACLF patients, higher levels of procalcitonin (PCT), lower levels of albumin, decreased prothrombin activity and deceased patients were associated with lower expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. Peripheral blood mononuclear cells (PBMCs), after removing adherent cells, were co-cultured with monocyte-derived DC. Our study revealed that patients with infection and low albumin levels exhibited a decreased proportion of T cell subsets within PBMCs. Additionally, these patients' T cells showed lower levels of Ki-67 and interferon-gamma (IFN-γ) production. Conclusion: ACLF patients exhibit varying clinical states, with differences in the phenotype and the ability of monocyte-derived dendritic cells to stimulate T cells. Alcohol can stimulate the maturation of monocyte-derived dendritic cells.

Development of a nomogram for the prediction of acute kidney injury after liver transplantation: a model based on clinical parameters and postoperative cystatin C level.

BACKGROUND: Acute kidney injury (AKI) is common after liver transplantation (LT). We developed a nomogram model to predict post-LT AKI. METHODS: A total of 120 patients were eligible for inclusion in the study. Clinical information was extracted from the institutional electronic medical record system. Blood samples were collected prior to surgery and immediately after surgery. Univariable and multivariate logistic regression were used to identify independent risk factors. Finally, a nomogram was developed based on the final multivariable logistic regression model. RESULTS: In total, 58 (48.3%) patients developed AKI. Multivariable logistic regression revealed four independent risk factors for post-LT AKI: operation duration [odds ratio (OR) = 1.728, 95% confidence interval (CI) = 1.121-2.663, p = 0.013], intraoperative hypotension (OR = 3.235, 95% CI = 1.316-7.952, p = 0.011), postoperative cystatin C level (OR = 1.002, 95% CI = 1.001-1.004, p = 0.005) and shock (OR = 4.002, 95% CI = 0.893-17.945, p = 0.070). Receiver operating characteristic curve analysis was used to evaluate model discrimination. The area under the curve value was 0.815 (95% CI = 0.737-0.894). CONCLUSION: The model based on combinations of clinical parameters and postoperative cystatin C levels had a higher predictive performance for post-LT AKI than the model based on clinical parameters or postoperative cystatin C level alone. Additionally, we developed an easy-to-use nomogram based on the final model, which could aid in the early detection of AKI and improve the prognosis of patients after LT.

Acute kidney injury (AKI) is one of the most common and important complications after liver transplantation (LT).We developed a nomogram model to predict post-LT AKI based on clinical parameters and postoperative cystatin C level.The model based on combinations of clinical parameters and postoperative cystatin C levels had a higher predictive performance, which could aid in the early detection of AKI and improve the prognosis of patients after LT.

TGFß1-RCN3-TGFBR1 loop facilitates pulmonary fibrosis by orchestrating fibroblast activation.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) bears high mortality due to unclear pathogenesis and limited therapeutic options. Therefore, identifying novel regulators is required to develop alternative therapeutic strategies. METHODS: The lung fibroblasts from IPF patients and Reticulocalbin 3 (RCN3) fibroblast-selective knockdown mouse model were used to determine the importance of Rcn3 in IPF; the epigenetic analysis and protein interaction assays, including BioID, were used for mechanistic studies. RESULTS: Reticulocalbin 3 (RCN3) upregulation is associated with the fibrotic activation of lung fibroblasts from IPF patients and Rcn3 overexpression blunts the antifibrotic effects of pirfenidone and nintedanib. Moreover, repressing Rcn3 expression in mouse fibroblasts ameliorates bleomycin-induced lung fibrosis and pulmonary dysfunction in vivo. Mechanistically, RCN3 promotes fibroblast activation by maintaining persistent activation of TGFß1 signalling via the TGFß1-RCN3-TGFBR1 positive feedback loop, in which RCN3 upregulated by TGFß1 exposure detains EZH2 (an epigenetic methyltransferase) in the cytoplasm through RCN3-EZH2 interaction, leading to the release of the EZH2-H3K27me3 epigenetic repression of TGFBR1 and the persistent expression of TGFBR1. CONCLUSIONS: These findings introduce a novel regulating mechanism of TGFß1 signalling in fibroblasts and uncover a critical role of the RCN3-mediated loop in lung fibrosis. RCN3 upregulation may cause resistance to IPF treatment and targeting RCN3 could be a novel approach to ameliorate pulmonary fibrosis.

Real-World Effectiveness of Nirmatrelvir/Ritonavir and Dexamethasone Among Hospitalized Patients with COVID-19: A Prospective Cohort Study.

Purpose: Anti-viral and anti-inflammatory therapies were effective in altering virus repletion and immune dysregulation in Coronavirus Disease 2019 (COVID-19) patients. This study aimed to explore the effect of combination therapy on disease progression in a real-world setting. Patients and Methods: A total of 836 patients confirmed with SARS-CoV-2 infection participated in the study from 15 November to 25 December 2022 at Beijing Youan Hospital, Capital Medical University. A prospective cohort study was implemented to investigate the prognostic effect of the combination therapy on virus shedding and clinical recovery. Results: About 78% of patients used nirmatrelvir/ritonavir (N/R, Paxlovid®, Pfizer) negatively, 16% of patients were prescribed nirmatrelvir/ritonavir beyond five days of symptom onset, 4% of patients received N/R monotherapy within five days of symptom onset and 2% of patients received N/R combined with dexamethasone. Compared with untreated patients, N/R monotherapy reduced the median time to 10.0 days from 12.0 days according to the negative conversion of nucleic acid amplification test (NAAT), and combination therapy reduced the time to 7.0 days, and increased to a 1.99 (95% CI 0.92, 4.32) and 14.23-fold (95% CI 4.50, 44.95) probability of negative NAAT, respectively. N/R monotherapy reduced the clinical recovery time to 10.0 days from 13.0 days. Single-use and combined-use non-significantly increased the recovery probability by 61% and 69%, respectively. In mild and moderate patients, the HRs for clinical recovery increased to 1.69 (95% CI 0.73, 3.94) and 2.18 (95% CI 0.29, 16.62), respectively. Conclusion: Combination therapy of N/R and dexamethasone increased negative conversion of NAAT and was associated with a non-significant improvement in clinical recovery. Further studies are warranted to confirm this efficacy.

Corrigendum: Synergistic effect of GF9 and streptomycin on relieving gram-negative bacteria-induced sepsis.

[This corrects the article DOI: 10.3389/fbioe.2022.973588.].

Clinical characteristics of adult inpatients with Measles in Beijing from 2010 to 2021: a retrospective analysis.

BACKGROUND: With the measles vaccine coverage rate gradually increasing, adult patients' epidemiological and clinical characteristics have changed. AIMS: To analyze the clinical characteristics of adult measles patients in Beijing Youan Hospital. METHODS: We retrospectively reviewed the electronic medical records of 818 patients diagnosed with measles at Beijing Youan Hospital between June 2010 and October 2021. We divided all hospitalized patients into two demographics groups, using 14 years of age as the cut-off. RESULTS: Of the adult inpatients, 110 (74.83%) were aged 20-40. There was an overall peak incidence in 2014, and yearly peaks came in April. Fever, cough, erythema, and Koplik's spots were present in 79.59%, 82.1%, 99.3%, and 59.8% of the adult group, respectively, compared to 75.26%, 92.0%, 99.9%, and 39.0% of the pediatric group. Decreased lymphocytes and hepatic impairment were common in adults. The adult group's median level of C-reactive protein was higher than that of the pediatric group (p < 0.05). The positive rate of measles antibody (IgM) detection was 64.6% in the adults and 78.8% in the pediatric group (p < 0.05). Of the adults, 46.9%, 8.8%, and 66% had pneumonia, gastroenteritis, and antibiotic use, compared to 89.6%, 2.7%, and 83.2% of the pediatric patients. The duration of symptoms before admission and the average length of hospital stay was approximately six days in both groups. CONCLUSIONS: Koplik's spots are more likely to be detected by clinicians in adult patients admitted to the hospital. Active surveillance is helpful for adults who are negative for IgM on admission. Although the proportion of adult measles patients with liver injury is high, the disease is generally mild. Measles significantly impacts peripheral blood lymphocytes in adults, but adults are at lower risk of concurrent pneumonia than the pediatric group. Clinicians need to pay attention to the appropriate use of antibiotics. Expanding the coverage of the measles vaccination in high-risk areas is beneficial for preventing measles in adults.

Serum Rcn3 level is a potential diagnostic biomarker for connective tissue disease-associated interstitial lung disease and reflects the severity of pulmonary function.

BACKGROUND: Although reticulocalbin 3 (Rcn3) has a critical role in alveolar epithelial function as well as in pathogenesis of pulmonary fibrosis, no study has yet examined its diagnostic and prognostic values for interstitial lung disease (ILD). This study aimed to evaluate Rcn3 as a potential marker in differential diagnosis of idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) and in reflecting the severity of disease. METHODS: This was a retrospective observational pilot study included 71 ILD patients and 39 healthy controls. These patients were stratified into IPF group (39) and CTD-ILD group (32). The severity of ILD was evaluated through pulmonary function test. RESULTS: Serum Rcn3 level was statistically higher in CTD-ILD patients than that in IPF patients (p = 0.017) and healthy controls (p = 0.010). Serum Rcn3 further showed statistically negative correlation with pulmonary function indexes (TLC% pred and DLCO% pred) and positive correlation with inflammatory indexes (CRP and ESR) (r = - 0.367, p = 0.039; r = - 0.370, p = 0.037; r = 0.355, p = 0.046; r = 0.392, p = 0.026, respectively) in CTD-ILD patients rather than IPF patients. ROC analysis demonstrated that serum Rcn3 had superior diagnostic value for CTD-ILD and a cutoff value of 2.73 ng/mL had a sensitivity of 69%, a specificity of 69% and an accuracy of 45% for diagnose of CTD-ILD. CONCLUSIONS: Serum Rcn3 levels might be a clinically useful biomarker in screening and evaluating CTD-ILD.

CRISPR/Cas13a-assisted rapid and portable HBV DNA detection for low-level viremia patients.

BACKGROUND & AIMS: The WHO declared to eliminate hepatitis B virus (HBV) by 2030. However, an increasing number of patients are presenting with low-level viremia (LLV) with the widespread use of antiviral medications. The diagnostic efficiency and coverage area of HBV infection are low. Hence, this study intended to drive the HBV infection detection to effectively adaptable for any small to medium-sized laboratory or field survey. METHODS: We established, optimized, and evaluated a colloidal gold test strip for detection of HBV DNA based on CRISPR/Cas13a combined with recombinase-aided amplification (RAA) technology. Furthermore, 180 HBV-infected patients (including patients with different viral loads, LLV patients and dynamic plasma samples of patients on antiviral therapy) were enrolled for clinical validation. RESULTS: The strip detection of HBV DNA was established based on RAA-CRISPR-Cas13a technology with a sensitivity of 101 copies/µL and a specificity of 100%. HBV DNA gradient concentration plasmids and clinical samples were effectively identified by this approach. The positive coincidence rate for LLV patients was 87%, while the negative coincidence rate was 100%. The positive coincidence rate reached 100% in LLV patients (viral loading >100 IU/mL). The sensitivity, specificity, positive predictive agreement (PPA) and negative predictive agreement (NPA) values of dynamic plasma detection in patients on antiviral therapy were 100%, 92.15%, 93.75%, and 100%, respectively. CONCLUSIONS: We develop rapid and portable RAA-CRISPR/Cas13a-based strip of HBV DNA detection for LLV patients. This study provides a visual and faster alternative to current PCR-based diagnosis for HBV infection.

Application of deep learning-based diagnostic systems in screening asymptomatic COVID-19 patients among oversea returnees.

INTRODUCTION: Our study aimed to investigate the performance of deep learning (DL)-based diagnostic systems in alerting against COVID-19, especially among asymptomatic individuals coming from overseas, and to analyze the features of identified asymptomatic patients in detail. METHODOLOGY: DL diagnostic systems were deployed to assist in the screening of COVID-19, including the pneumonia system and pulmonary nodules system. 1,917 overseas returnees who underwent CT examination and rRT-PCR tests were enrolled. DL pneumonia system promptly alerted clinicians to suspected COVID-19 after CT examinations while the performance was evaluated with rRT-PCR results as the reference. The radiological features of asymptomatic COVID-19 cases were described according to the Nomenclature of the Fleischner Society. RESULTS: Fifty-three cases were confirmed as COVID-19 patients by rRT-PCR tests, including 5 asymptomatic cases. DL pneumonia system correctly alerted 50 cases as suspected COVID-19 with a sensitivity of 0.9434 and specificity of 0.9592 (within 2 minutes per case); while the pulmonary nodules system alerted 2 of the 3 missed asymptomatic cases. Additionally, five asymptomatic patients presented different characteristics such as elevated creatine kinase level and prolonged prothrombin time, as well as atypical radiological features. CONCLUSIONS: DL diagnostic systems are promising complementary approaches for prompt screening of imported COVID-19 patients, even the imported asymptomatic cases. Unique clinical and radiological characteristics of asymptomatic cases might be of great value in screening as well. ADVANCES IN KNOWLEDGE: DL-based systems are practical, efficient, and reliable to assist radiologists in screening COVID-19 patients. Differential features of asymptomatic patients might be useful to clinicians in the frontline to differentiate asymptomatic cases.

Identification of purine biosynthesis as an NADH-sensing pathway to mediate energy stress.

An enhanced NADH/NAD+ ratio, termed reductive stress, is associated with many diseases. However, whether a downstream sensing pathway exists to mediate pathogenic outcomes remains unclear. Here, we generate a soluble pyridine nucleotide transhydrogenase from Escherichia coli (EcSTH), which can elevate the NADH/NAD+ ratio and meantime reduce the NADPH/NADP+ ratio. Additionally, we fuse EcSTH with previously described LbNOX (a water-forming NADH oxidase from Lactobacillus brevis) to resume the NADH/NAD+ ratio. With these tools and by using genome-wide CRISPR/Cas9 library screens and metabolic profiling in mammalian cells, we find that accumulated NADH deregulates PRPS2 (Ribose-phosphate pyrophosphokinase 2)-mediated downstream purine biosynthesis to provoke massive energy consumption, and therefore, the induction of energy stress. Blocking purine biosynthesis prevents NADH accumulation-associated cell death in vitro and tissue injury in vivo. These results underscore the pathophysiological role of deregulated purine biosynthesis in NADH accumulation-associated disorders and demonstrate the utility of EcSTH in manipulating NADH/NAD+ and NADPH/NADP+.

Synergistic effect of GF9 and streptomycin on relieving gram-negative bacteria-induced sepsis.

Triggering receptor expressed on myeloid cells-1 (TREM-1) regulates inflammation and promotes a vigorous immune response. GF9 is one of the peptides that inhibit the mTREM-1 signaling pathway, thus reducing the inflammatory mediators in diseases including sepsis. Nanotechnology could offer a new complementary strategy for diseases. Streptomycin is also one treatment of sepsis. However, the role of nanoparticles delivered GF9 combined with streptomycin on sepsis had never been discovered. In the present study, cecal ligation and puncture (CLP) and lipopolysaccharide [LPS, Escherichia coli (E. coli) O111:B4] sepsis models were constructed. SDS-PAGE was used to evaluate the size of nano drugs; Western blot was used to detect the protein levels of MMP2 and TREM-1 in cells. The levels of TNF-α and IL-6 were detected by ELISA. Histopathological changes were observed by HE staining. And the nanomedicines of GF9-HFn/Str were successfully constructed. The size of GF9-HFn/Str is 36 kD. The ferritin-based nanoparticle plays a vital role in delivering streptomycin into cells and tissues. GF9 (1.6 µM) and streptomycin (40 µM) co-delivery nanomedicine showed a better effect on promoting overall survival, decreasing E. coli, significantly suppressed the expression levels of inflammatory factors (TNF-α and IL-6), and can reduce lung injury. Our study demonstrated that combination delivery of nanomedicine GF9 and streptomycin have a better effect on overall survival rate, anti-inflammatory, and anti-bacterial in sepsis. Our present study revealed a new potential therapeutic method for sepsis.