Clinical significance of lower respiratory tract culture within 48 h of admission in patients with viral pneumonia: an observational study.

BACKGROUND: The aim of this retrospective study was to examine the risk factors of positive lower respiratory tract cultures and to investigate whether nosocomial infections are common in patients with positive lower respiratory tract cultures. METHODS: We enrolled 86 patients diagnosed with influenza A-related critical illness who were treated at Fuzhou Pulmonary Hospital of Fujian in China between 1st October 2013 and 31st March 2019. The of admission were used to divide the enrolled patients into two groups. Sputum and bronchoalveolar lavage fluid specimens were collected within 48 h after admission for culture. All samples were cultured immediately after sampling. Nosocomial infections are defined as any symptom or sign of pulmonary infiltration, confirmed by X-ray, after 5 days of admission and positive results from one or more cultures. RESULTS: The average age of this cohort was (54.13 ± 16.52) years. Based on the culture results, Staphylococcus aureus and Candida albicans had the highest positive rates (3.40% (3/86) and 20.90% (18/86), respectively). In patients with positive lower respiratory tract cultures, the incidence of nosocomial infection was 73.30% (22/30) five days after admission. However, the incidence of nosocomial infection was lower (42.80%, 24/56) in patients with negative lower respiratory tract cultures. Hemoptysis, systolic pressure at admission, and blood urea nitrogen level at admission were all independent risk factors for positive lower respiratory tract cultures within 48 h of admission. CONCLUSION: Our data showed that a significant proportion of patients with pneumonia exhibited co-infections with bacteria or fungi within five days of hospital admission. Hemoptysis, systolic pressure, and blood urea nitrogen levels at admission emerged as the key risk factors. These findings underscore the necessity of closely monitoring patients with influenza infection, particularly for positive bacterial or fungal cultures within the initial 48 h of admission.

Base-Promoted Decarboxylative Annulation of Methyl 2-(2-Bromophenyl)acetates and Ynones to Access Benzoxepines.

A simple and efficient base-mediated decarboxylative annulation of ynones with methyl 2-(2-bromophenyl)acetates has been developed. A broad range of benzoxepines were prepared with a broad substrate scope and high regioselectivity in moderate to excellent yields under transition-metal-free conditions. This method proceeds through a tandem [2 + 4] annulation, ring-opening decarboxylative reaction, and the intramolecular nucleophilic aromatic substitution reaction. Additionally, the key intermediates were successfully obtained and characterized unambiguously by single-crystal X-ray crystallography, which could favorably support a decarboxylative annulation mechanism. Furthermore, gram-scale reaction and synthetic applications for the further functionalization are also studied.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Noninvasive Mechanical Ventilation in Patients with Viral Pneumonia-Associated Acute Respiratory Distress Syndrome: An Observational Retrospective Study.

Objectives: Appropriate mechanical ventilation may change the prognosis of patients with viral pneumonia-associated acute respiratory distress syndrome (ARDS). This study aimed to identify the factors associated with the success of noninvasive ventilation in the management of patients with ARDS secondary to respiratory viral infection. Methods: In this retrospective cohort study, all patients with viral pneumonia-associated ARDS were divided into the noninvasive mechanical ventilation (NIV) success group and the NIV failure group. The demographic and clinical data of all patients were collected. The factors associated with the success of noninvasive ventilation were identified by the logistic regression analysis. Results: Among this cohort, 24 patients with an average age of 57.9 ± 17.0 years received successful NIVs, and NIV failure occurred in 21 patients with an average age of 54.1 ± 14.0 years. The independent influencing factors for the success of the NIV were the acute physiology and chronic health evaluation (APACHE) II score (odds ratio (OR): 1.83, 95% confidence interval (CI): 1.10-3.03) and lactate dehydrogenase (LDH) (OR: 1.011, 95% CI: 1.00-1.02). When the oxygenation index (OI) is <95 mmHg, APACHE II > 19, and LDH > 498 U/L, the sensitivity and specificity of predicting a failed NIV were (66.6% (95% CI: 43.0%-85.4%) and 87.5% (95% CI: 67.6%-97.3%)); (85.7% (95% CI: 63.7%-97.0%) and 79.1% (95% CI: 57.8%-92.9%)); (90.4% (95% CI: 69.6%-98.8%) and 62.5% (95% CI: 40.6%-81.2%)), respectively. The areas under the receiver operating characteristic curve (AUC) of the OI, APACHE II scores, and LDH were 0.85, which was lower than the AUC of the OI combined with LDH and the APACHE II score (OLA) of 0.97 (P=0.0247). Conclusions: Overall, patients with viral pneumonia-associated ARDS receiving successful NIV have lower mortality rates than those for whom NIV failed. In patients with influenza A-associated ARDS, the OI may not be the only indicator of whether NIV can be used; a new indicator of NIV success may be the OLA.

Near-Infrared-II Quantum Dots for In Vivo Imaging and Cancer Therapy.

In vivo fluorescence imaging can perform real-time, noninvasive, and high spatiotemporal resolution imaging to accurately obtain the dynamic biological information in vivo, which plays significant roles in the early diagnosis and treatment of cancer. However, traditional in vivo fluorescence imaging usually operates in the visible and near-infrared (NIR)-I windows, which are severely interfered by the strong tissue absorption, tissue scattering, and autofluorescence. The emergence of NIR-II imaging at 1000-1700 nm significantly breaks through the imaging limitations in deep tissues, due to less tissue scattering and absorption. Benefiting from the outstanding optical properties of NIR-II quantum dots (QDs), such as high brightness and good photostability, in vivo fluorescence imaging exhibits excellent temporal-spatial resolution and large penetration depth, and QDs have become a kind of promising fluorescent biomarkers in the field of in vivo fluorescence imaging. Herein, the authors review NIR-II QDs from preparation to modification, and summarize recent applications of NIR-II QDs, including in vivo imaging and imaging-guided therapies. Finally, they discuss the special concerns when NIR-II QDs are shifted from in vivo imaging applications to further in-depth applications.

Spatiotemporal Quantification of Endosomal Acidification on the Viral Journey.

Many enveloped viruses utilize endocytic pathways and vesicle trafficking to infect host cells, where the acidification of virus-containing endosomes triggers the virus-endosome fusion events. Therefore, simultaneous correlation of intracellular location, local pH, and individual virus dynamics is important for gaining insight into viral infection mechanisms. Here, an imaging approach is developed for spatiotemporal quantification of endosomal acidification on the viral journey in host cells using a fluorescence resonance energy transfer based ratiometric pH sensor consisting of a photostable and high-brightness QD, pH-sensitive fluorescent dyes, and virus-binding proteins. Ratiometric analysis of sensor-based single-virus tracking data enables to dissect a two-step endosomal acidification process during the infection of influenza viruses and elucidates the occurrence of the fission and sorting of virus-containing endosomes to recycling endosomes after initial acidification. This technique should serve as a robust approach for in situ quantification of endosomal acidification on the viral journey.

Comparison of Conduits Fabricated by Fresh and Predegenerated Skeletal Muscles for Peripheral Nerve Repairing.

ABSTRACT: Reconstruction of peripheral nerve injury remains a challenge for clinical medicine. Previous reports have confirmed that external oblique muscle-fabricated nerve conduit (EMC) could effectively be used to promote peripheral nerve regeneration. In this study, we compared between conduits fabricated from fresh muscle and conduits fabricated from predegenerated muscle for the repair of peripheral nerve defects in a mouse sciatic nerve transection model. We found that the number, diameter, and myelin sheath thickness of the myelinated nerve fibers of the regenerative nerve in the EMC group were larger than those of the predegenerated-EMC (P-EMC) group eight weeks after surgery. The sciatic function index and gastrocnemius wet-weight mass ratio in the EMC group were higher than those in the P-EMC group. The Bcl-2/Bax ratio and the number of Schwann cell nucleus in the proximal nerve stumps in the EMC group were greater than those in the P-EMC group. In conclusion, our results confirmed that the use of fresh skeletal muscle nerve conduit increased the Bcl-2/Bax ratio and promoted the survival of Schwann cells of the proximal nerve stump compared with that of predegenerated skeletal muscle nerve conduits, thus achieving better functional recovery after sciatic nerve defect.

Catalyst- and Additive-Free Annulation of Ynediones and (Iso)Quinoline N-Oxides: An Approach to Synthesis of Pyrrolo[2,1-a]Isoquinolines and Pyrrolo[1,2-a]Quinolines.

A simple and effective annulation of ynediones and (iso)quinoline N-oxides was developed to afford various functionalized pyrrolo[2,1-a]isoquinolines and pyrrolo[1,2-a]quinolines in moderate to excellent yields. This protocol underwent a tandem [3 + 2] cycloaddition/ring-opening/N-nucleophilic addition, which exhibited high regioselectivity, broad substrate tolerance, and atom economy under catalyst-, additive-free, and air conditions. Moreover, indolizine was also successfully prepared using pyridine N-oxide.

A novel diagnostic method for pituitary adenoma based on magnetic resonance imaging using a convolutional neural network.

PURPOSE: This study was designed to develop a computer-aided diagnosis (CAD) system based on a convolutional neural network (CNN) to diagnose patients with pituitary tumors. METHODS: We included adult patients clinically diagnosed with pituitary adenoma (pituitary adenoma group), or adult individuals without pituitary adenoma (control group). After pre-processing, all the MRI data were randomly divided into training or testing datasets in a ratio of 8:2 to create or evaluate the CNN model. Multiple CNNs with the same structure were applied for different types of MR images respectively, and a comprehensive diagnosis was performed based on the classification results of different types of MR images using an equal-weighted majority voting strategy. Finally, we assessed the diagnostic performance of the CAD system by accuracy, sensitivity, specificity, positive predictive value, and F1 score. RESULTS: We enrolled 149 participants with 796 MR images and adopted the data augmentation technology to create 7960 new images. The proposed CAD method showed remarkable diagnostic performance with an overall accuracy of 91.02%, sensitivity of 92.27%, specificity of 75.70%, positive predictive value of 93.45%, and F1-score of 92.67% in separate MRI type. In the comprehensive diagnosis, the CAD achieved better performance with accuracy, sensitivity, and specificity of 96.97%, 94.44%, and 100%, respectively. CONCLUSION: The CAD system could accurately diagnose patients with pituitary tumors based on MR images. Further, we will improve this CAD system by augmenting the amount of dataset and evaluate its performance by external dataset.

TLR4/AP-1-Targeted Anti-Inflammatory Intervention Attenuates Insulin Sensitivity and Liver Steatosis.

Insulin resistance has been shown to be the common pathogenesis of many metabolic diseases. Metainflammation is one of the important characteristics of insulin resistance. Macrophage polarization mediates the production and development of metainflammation. Toll-like receptor 4 (TLR4) mediates macrophage activity and is probably the intersection of immunity and metabolism, but the detailed mechanism is probably not fully understood. Activated protein 1 (AP1) signaling pathway is very important in macrophage activation-mediated inflammation. However, it is unclear whether AP1 signaling pathway mediates metabolic inflammation in the liver. We aimed to investigate the effects of macrophage TLR4-AP1 signaling pathway on hepatocyte metabolic inflammation, insulin sensitivity, and lipid deposition, as well as to explore the potential of TLR4-AP1 as new intervention targets of insulin resistance and liver steatosis. TLR4 and AP1 were silenced in the RAW264.7 cells by lentiviral siRNA transfection. In vivo transduction of lentivirus was administered in mice fed with high-fat diet. Insulin sensitivity and inflammation were evaluated in the treated cells or animals. Our results indicated that TLR4/AP-1 siRNA transfection alleviated high-fat diet-induced systemic and hepatic inflammation, obesity, and insulin resistance in mice. Additionally, TLR4/AP-1 siRNA transfection mitigated palmitic acid- (PA-) induced inflammation in RAW264.7 cells and metabolic abnormalities in cocultured AML hepatocytes. Herein, we propose that TLR4-AP1 signaling pathway activation plays a crucial role in high fat- or PA-induced metabolic inflammation and insulin resistance in hepatocytes. Intervention of the TLR4 expression regulates macrophage polarization and metabolic inflammation and further alleviates insulin resistance and lipid deposition in hepatocytes.