Application of deep learning to pressure injury staging.

OBJECTIVE: Accurate assessment of pressure injuries (PIs) is necessary for a good outcome. Junior and non-specialist nurses have less experience with PIs and lack clinical practice, and so have difficulty staging them accurately. In this work, a deep learning-based system for PI staging and tissue classification is proposed to help improve its accuracy and efficiency in clinical practice, and save healthcare costs. METHOD: A total of 1610 cases of PI and their corresponding photographs were collected from clinical practice, and each sample was accurately staged and the tissues labelled by experts for training a Mask Region-based Convolutional Neural Network (Mask R-CNN, Facebook Artificial Intelligence Research, Meta, US) object detection and instance segmentation network. A recognition system was set up to automatically stage and classify the tissues of the remotely uploaded PI photographs. RESULTS: On a test set of 100 samples, the average precision of this model for stage recognition reached 0.603, which exceeded that of the medical personnel involved in the comparative evaluation, including an enterostomal therapist. CONCLUSION: In this study, the deep learning-based PI staging system achieved the evaluation performance of a nurse with professional training in wound care. This low-cost system could help overcome the difficulty of identifying PIs by junior and non-specialist nurses, and provide valuable auxiliary clinical information.

DNA and RNA editing without sequence limitation using the flap endonuclease 1 guided by hairpin DNA probes.

Here, we characterized a flap endonuclease 1 (FEN1) plus hairpin DNA probe (hpDNA) system, designated the HpSGN system, for both DNA and RNA editing without sequence limitation. The compact size of the HpSGN system make it an ideal candidate for in vivo delivery applications. In vitro biochemical studies showed that the HpSGN system required less nuclease to cleave ssDNA substrates than the SGN system we reported previously by a factor of ∼40. Also, we proved that the HpSGN system can efficiently cleave different RNA targets in vitro. The HpSGN system cleaved genomic DNA at an efficiency of ∼40% and ∼20% in bacterial and human cells, respectively, and knocked down specific mRNAs in human cells at a level of ∼25%. Furthermore, the HpSGN system was sensitive to the single base mismatch at the position next to the hairpin both in vitro and in vivo. Collectively, this study demonstrated the potential of developing the HpSGN system as a small, effective, and specific editing tool for manipulating both DNA and RNA without sequence limitation.

Maintaining normal sleep patterns, lifestyles and emotion during the COVID-19 pandemic: The stabilizing effect of daytime napping.

This study aimed to assess changes in sleep pattern and their influence on people's daily life and emotion during the COVID-19 pandemic. Self-developed questionnaires were used to measure changes in nocturnal sleep, daytime napping, lifestyles and negative emotions in individuals before and after the COVID-19 pandemic. Nine hundred and thirty effective questionnaires were collected in this study. Repeated measures analysis of variance and hierarchical regression analysis were applied. We found that individuals' sleep rhythms were delayed, and sleep duration and sleep latency were increased during the stay-at-home orders. Meanwhile, their exercise levels and learning/working efficiency were decreased, and electronic device use time, annoyance levels and anxiety levels were increased. Delayed sleep patterns affected lifestyles and emotions. Moreover, sleep quality positively predicted learning/working efficiency and exercise levels, and negatively predicted use of electronic devices and negative emotions. Sleep patterns became delayed on weekdays during stay-at-home orders in all four daytime napping groups (no daytime napping, daytime napping as before, more daytime napping and less daytime napping), and the group taking daytime naps as before had a minimal variation, and their lifestyles and emotions were significantly better than those of the other groups. This study demonstrated that under the influence of stress caused by the pandemic, maintaining regular daytime napping was an effective way to stabilize sleep patterns and biological rhythms, keep good lifestyles and alleviate the effect of acute psychological stress, and to prevent and control mental disorders during the pandemic.

Chronotype and depressive symptoms: A moderated mediation model of sleep quality and resilience in the 1st-year college students.

OBJECTIVE: Depression is highly prevalent among 1st-year college students, and evening chronotype is an important risk factor associated with depression. This study investigates the mediating role of sleep quality and the moderating role of resilience between chronotype and depressive symptoms. METHODS: A total of 4531 students were included in this cross-sectional study. Mediation and moderated mediation models were applied. RESULTS: The association between chronotype and depressive symptoms was partially mediated by sleep quality, and the direct and indirect effects were moderated by resilience. The negative correlation between chronotype and depressive symptoms was significant in students with low levels of resilience compared with moderate/high levels. The positive correlation between sleep quality and depressive symptoms was strongest in low-level resilience students. CONCLUSION: This study reveals that greater eveningness is associated with poorer sleep quality among 1st-year college students, which may lead to severer depression, and highlights the importance of resilience training in reducing depressive symptoms.

G1 phase cell cycle arrest in NSCLC in response to LZ-106, an analog of enoxacin, is orchestrated through ROS overproduction in a P53-dependent manner.

LZ-106, a newly synthetized analog of quinolone, has been shown to be highly effective in non-small cell lung cancer (NSCLC) in both cultured cells and xenograft mouse model with low toxicity, yet the molecular mechanisms still require exploration. Here, we substantiated the involvement of P53 activation in intracellular reactive oxygen species (ROS) generation upon LZ-106 treatment and related P53 to the ROS-induced viability inhibition and apoptosis, which was exhibited in the previous research. P53 was shown to play an indispensable role in the elevated levels of intracellular ROS in LZ-106-treated NSCLC cells through ROS detection. We further identified the anti-proliferation effect of LZ-106 in NSCLC cells through G1 phase cell cycle arrest by cell cycle analysis, with the expression analysis of the key proteins, and discovered that the cell cycle arrest effect is also mediated by induction of ROS in a P53-dependent manner. In addition, the tumor suppression effect exhibited in vivo was demonstrated to be similar to that in vitro, which requires the participation of P53. Thus, LZ-106 is a potent antitumor drug possessing potent proliferation inhibition and apoptosis induction ability through the P53-dependent ROS modulation both in vitro and in vivo.

Human adenovirus load in respiratory tract secretions are predictors for disease severity in children with human adenovirus pneumonia.

BACKGROUND: Pneumonia is a serious public health issue and is concerned around the world. This study is to investigate the association between viral load in children with human adenovirus (HAdV) pneumonia and disease severity. METHODS: A total of 1313 cases of children hospitalized in Hunan Provincial People's Hospital due to community acquired pneumonia (CAP) from April 2011 to May 2014 were enrolled in this study. Samples of nasopharyngeal aspirate were collected for the cohort. WHO criteria for CAP grading was emerged for pneumonia severity classification. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect 12 kinds of respiratory viruses. HAdV types were identified by nested PCR. The relationship between HAdV load and severity of disease was there by analyzed. RESULTS: Finally, 174 cases (174/1313, 13.3%) were positive for HAdV, and HAdV type 7 (HAdV-7) was the main serotype (76/174, 43.7%). Among the 174 cases, 70 cases were with HAdV infection alone and 104 cases were accompanied by other viruses. The patients were divided into mild pneumonia group (n = 108 cases) and severe pneumonia group (n = 66 cases). HAdV load of children in severe pneumonia group was higher than that in mild pneumonia group. Similar result was obtained in the 70 cases with HAdV infection alone after subgrouping. Relevant factors analysis results showed that severe pneumonia children presented lower onset age, more prone to fever, longer fever time, and longer hospital stay compared with that of mild pneumonia children. Children with HAdV-7 infection developed more frequently severe pneumonia. Multivariate regression analysis showed that HAdV load, age, and fever time were risk factors for pneumonia severity. CONCLUSION: The severity of HAdV infection is significantly correlated with viral load and serotype.

Accuracy of 16/18G core needle biopsy for ultrasound-visible breast lesions.

BACKGROUND: To assess the accuracy of ultrasound-guided 16G or 18G core needle biopsy (CNB) for ultrasound-visible breast lesions, and to analyze the effects of lesion features. METHODS: Between July 2005 and July 2012, 4,453 ultrasound-detected breast lesions underwent ultrasound-guided CNB and were retrospectively reviewed. Surgical excision was performed for 955 lesions (566 with 16G CNB and 389 with 18G CNB) which constitute the basis of the study. Histological findings were compared between the ultrasound-guided CNB and the surgical excision to determine sensitivity, false-negative rate, agreement rate, and underestimation rate, according to different lesion features. RESULTS: Final pathological results were malignant in 84.1% (invasive carcinoma, ductal carcinoma in situ, lymphoma, and metastases), high-risk in 8.4% (atypical lesions, papillary lesions, and phyllodes tumors), and benign in 7.5%. False-negative rates were 1.4% for 16G and 18G CNB. Agreement rates between histological findings of CNB and surgery were 92.4% for 16G and 92.8% for 18G CNB. Overall underestimate rates (high-risk CNB becoming malignant on surgery and ductal carcinoma in situ becoming invasive carcinoma) were 47.4% for 16G and 48.9% for 18G CNB. Agreements were better for mass lesions (16G: 92.7%; 18G: 93.7%) than for non-mass lesions (16G, 85.7%; 18G, 78.3%) (P <0.01). For mass lesions with a diameter ≤10 mm, the agreement rates (16G, 83.3%; 18G, 86.7%) were lower (P <0.01). CONCLUSIONS: Ultrasound-guided 16G and 18G CNB are accurate for evaluating ultrasound-visible breast mass lesions with a diameter >10 mm.

Hepatic Stellate Cell-Targeting Micelle Nanomedicine for Early Diagnosis and Treatment of Liver Fibrosis.

Diagnosing and treating liver fibrosis is a challenging yet crucial endeavor due to its complex pathogenesis and risk of deteriorating into cirrhosis, liver failure, and even hepatic cancer. Herein, a silica cross-linked micelles (SCLMs) based nano-system is developed for both diagnosing and treating liver fibrosis. The SCLMs are first modified with peptide CTCE9908 (CT-SCLMs) and can actively target CXCR4, which is overexpressed in activated hepatic stellate cells (HSCs). To enable diagnosis, an ONOO--responded near-infrared fluorescent probe NOF2 is loaded into the CT-SCLMs. This nano-system can target the aHSCs and diagnose the liver fibrosis particularly in CCl4-induced liver damage, by monitoring the reactive nitrogen species. Furthermore, a step is taken toward treatment by co-encapsulating two anti-fibrosis drugs, silibinin and sorafenib, within the CT-SCLMs. This combined approach results in a significant alleviation of liver injury. Symptoms associated with liver fibrosis, such as deposition of collagen, expression of hydroxyproline, and raised serological indicators show notable improvement. In summary, the CXCR4-targeted nano-system can serve as a promising theragnostic system of early warning and diagnosis for liver fibrosis, offering hope against progression of this serious liver condition.

[Underestimation of papillary breast lesions at ultrasound-guided breast biopsy].

OBJECTIVE: To evaluate the underestimation of papillary breast lesions diagnosed at ultrasound-guided breast biopsy. METHODS: Totally 4453 ultrasound-guided visible breast lesions that were identified in the Department of Ultrasound, Chinese PLA General Hospital, from April 2005 to April 2012 were retrospectively reviewed. Of 207 papillary lesions that were detected by histologic findings of ultrasound-guided core needle biopsy(US-CNB), 90 underwent surgical excision, 110 were followed up for at least one year, and 7 were lost to follow-up. The histological findings of the US-CNB and the findings of surgical excision were compared to analyze the underestimation rates according to the Breast Imaging Reporting and Data System(BI-RADS)categories of American College of Radiology(ACR)and biopsy methods. RESULTS: Of the 90 papillary lesions underwent surgical excision, 29(32.2%)were underestimated, and 22 malignant lesions were underestimated(24.4%). Of the 23 papillomata with atypical ductal hyperplasia(IDP+ADH), 11(47.8%)were upgraded to malignant. Of the 137 benign intraductal papilloma(IDP)with concordance imaging-histologic findings, 8 lesions were underestimated(5.8%), whereas 10 out of 25(40.0%)IDP with diacordant imaging-histologic findings were underestimated. In total, 17.9% understimation were biopsied by 18G core needle biopsy(CNB)(P=0.017)and 16.0% by 16G CNB(P=0.023), which were significantly higher than vacuum-assisted biopsy(VAB). CONCLUSIONS: VAB is more accurate than 16G or 18G CNB in detecting papillary breast lesions. For high underestimations of IDP+ADH and IDP with discordant imaging-histologic findings, VAB or surgical excisions should be performed.

Structure of the green heme isolated from allylbenzene-modified chloroperoxidase: A novel heme architecture implicating the mechanisms of CPO inactivation and epoxidation.

The chemical identification of the modified heme (the green heme) during chloroperoxidase catalyzed epoxidation of allylbenzene remains unestablished due to its high instability within the protein matrix, the absence of paramagnetically shifted signals, and the difficulty in obtaining crystals of the modified enzyme. We have established the unambiguous structure of the modified prosthetic heme group, which was extracted from the protein matrix using 2D NMR spectroscopy and LC-MS spectrometry. The modified heme was isolated as a µ-oxo dimer that can be quantitatively converted to the corresponding monomer. The depolymerized green heme displayed characteristic NMR signatures of iron porphyrin complexes, but no Nuclear Overhauser Effect was observable to assist in signal assignment. An alternative strategy was applied by removing the iron center of the green heme, resulting in a stable demetallated green porphyrin species. Complete assignment of all the NMR resonances in the demetallated green heme allowed us to establish the molecular architecture of the modified species as a novel N-alkylated heme. Decisive space correlations between the propyl protons of allylbenzene and the γ meso proton coupled with clear dipolar connectivities between the propyl-2H of the substrate and the ß proton in the side chain of the propionic acid at carbon-6 of the porphyrin ring, clearly indicate that allylbenzene was covalently attached to the nitrogen atom of the pyrrole ring III of the prosthetic heme. In this study, the mechanism of green CPO formation and its relation to CPO catalyzed chiral transformations are also discussed. It is concluded that the double-phenyl clamp formed by two phenylalanine residues at the distal heme pocket plays a critical role in fine-tuning substrate orientation that determines the outcome of CPO catalyzed epoxidation of substituted styrenes.