Assessment and clinical utility of metagenomic next-generation sequencing for suspected lower respiratory tract infections.

OBJECTIVES: This study aims to compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) to traditional diagnostic methods in patients with lower respiratory tract infections (LRTIs), elucidate the etiological spectrum of these infections, and explore the impact of mNGS on guiding antimicrobial therapy. METHODS: We retrospectively analyzed data from 128 patients admitted to the Respiratory Department of Anqing 116 Hospital between July 2022 and July 2023. All patients had undergone both mNGS and conventional microbiological techniques (CMT) for LRTI diagnosis. We assessed the diagnostic performance of these methods and examined the influence of mNGS on antimicrobial decision-making. RESULTS: Overall, mNGS demonstrated superior sensitivity (96.8%) and accuracy (96.8%) compared to CMT. For Mycobacterium tuberculosis detection, the accuracy and sensitivity of mNGS was 88.8% and 77.6%, which was lower than the 94.7% sensitivity of the T-spot test and the 79.6% sensitivity of CMT. In fungal pathogen detection, mNGS showed excellent sensitivity (90.5%), specificity (86.7%), and accuracy (88.0%). Bacteria were the predominant pathogens detected (75.34%), with Mycobacterium tuberculosis (41.74%), Streptococcus pneumoniae (21.74%), and Haemophilus influenzae (16.52%) being most prevalent. Bacterial infections were most common (62.10%), followed by fungal and mixed infections (17.74%). Of the 118 patients whose treatment regimens were adjusted based on mNGS results, 102 (86.5%) improved, 7 (5.9%) did not respond favorably, and follow-up was lost for 9 patients (7.6%). CONCLUSIONS: mNGS offers rapid and precise pathogen detection for patients with suspected LRTIs and shows considerable promise in diagnosing Mycobacterium tuberculosis and fungal infections. By broadening the pathogen spectrum and identifying polymicrobial infections, mNGS can significantly inform and refine antibiotic therapy.

The burden of disease attributable to indoor air pollutants in China from 2000 to 2017.

BACKGROUND: High-level exposure to indoor air pollutants (IAPs) and their corresponding adverse health effects have become a public concern in China in the past 10 years. However, neither national nor provincial level burden of disease attributable to multiple IAPs has been reported for China. This is the first study to estimate and rank the annual burden of disease and the financial costs attributable to targeted residential IAPs at the national and provincial level in China from 2000 to 2017. METHODS: We first did a systematic review and meta-analysis of 117 articles from 37 231 articles identified in major databases, and obtained exposure-response relationships for the candidate IAPs. The exposure levels to these IAPs were then collected by another systematic review of 1864 articles selected from 52 351 articles. After the systematic review, ten IAPs with significant and robust exposure-response relationships and sufficient exposure data were finally targeted: PM2·5, nitrogen dioxide, sulphur dioxide, ozone, carbon monoxide, radon, formaldehyde, benzene, toluene, and p-dichlorobenzene. The annual exposure levels in residences were then evaluated in all 31 provinces in mainland China continuously from 2000 to 2017, using the spatiotemporal Gaussian process regression model to analyse indoor originating IAPs, and the infiltration factor method to analyse outdoor originating IAPs. The disability-adjusted life-years (DALYs) attributable to the targeted IAPs were estimated at both national and provincial levels in China, using the population attributable fraction method. Financial costs were estimated by an adapted human capital approach. FINDINGS: From 2000 to 2017, annual DALYs attributable to the ten IAPs in mainland China decreased from 4620 (95% CI 4070-5040) to 3700 (3210-4090) per 100 000. Nevertheless, in 2017, IAPs still ranked third among all risk factors, and their DALYs and financial costs accounted for 14·1% (95% CI 12·3-15·6) of total DALYs and 3·45% (3·01-3·82) of the gross domestic product. Specifically, the rank of ten targeted IAPs in order of their contribution to DALYs in 2017 was PM2·5, carbon monoxide, radon, benzene, nitrogen dioxide, ozone, sulphur dioxide, formaldehyde, toluene, and p-dichlorobenzene. The DALYs attributable to IAPs were 9·50% higher than those attributable to outdoor air pollution in 2017. For the leading IAP, PM2·5, the DALYs attributable to indoor origins are 18·3% higher than those of outdoor origins. INTERPRETATION: DALYs attributed to IAPs in China have decreased by 20·0% over the past two decades. Even so, they are still much higher than those in the USA and European countries. This study can provide a basis for determining which IAPs to target in various indoor air quality standards and for estimating the health and economic benefits of various indoor air quality control approaches, which will help to reduce the adverse health effects of IAPs in China. FUNDING: The National Key Research and Development Program of China and the National Natural Science Foundation of China.

[Meta-analysis of the Impact of Different Ozone Metrics on Total Mortality in China].

This study explores the effect of different ozone metrics on the total mortality risk in China. Using the CNKI, Wanfang, VIP, Web of Science, and PubMed databases, the time series studies and case crossover studies from the establishment of each database to December 31, 2020 were retrieved, and 22 eligible studies were included in this analysis. A meta-analysis was performed for the ozone metrics of O3-M1h, O3-M8h, and O3-24h. The results indicated that the increase in the total mortality risk is more closely associated with O3-M1h (RR #, 1.0052; 95%CI, 1.0031-1.0073) and is more weakly associated with O3-24h (RR #, 1.0036; 95%CI, 1.0025-1.0048) and O3-M8h (RR #, 1.0031; 95%CI, 1.0022-1.0041). A subgroup analysis of the three metrics revealed that the total mortality risk of ozone is higher in the cold season, the elderly (≥ 65) are more vulnerable to ozone pollution, and the total mortality risk in the north is higher than that in the south.

A comparative study of auto-contouring softwares in delineation of organs at risk in lung cancer and rectal cancer.

Radiotherapy requires the target area and the organs at risk to be contoured on the CT image of the patient. During the process of organs-at-Risk (OAR) of the chest and abdomen, the doctor needs to contour at each CT image. The delineations of large and varied shapes are time-consuming and laborious. This study aims to evaluate the results of two automatic contouring softwares on OARs definition of CT images of lung cancer and rectal cancer patients. The CT images of 15 patients with rectal cancer and 15 patients with lung cancer were selected separately, and the organs at risk were manually contoured by experienced physicians as reference structures. And then the same datasets were automatically contoured based on AiContour (version 3.1.8.0, Manufactured by Linking MED, Beijing, China) and Raystation (version 4.7.5.4, Manufactured by Raysearch, Stockholm, Sweden) respectively. Deep learning auto-segmentations and Atlas were respectively performed with AiContour and Raystation. Overlap index (OI), Dice similarity index (DSC) and Volume difference (Dv) were evaluated based on the auto-contours, and independent-sample t-test analysis is applied to the results. The results of deep learning auto-segmentations on OI and DSC were better than that of Atlas with statistical difference. There was no significant difference in Dv between the results of two software. With deep learning auto-segmentations, auto-contouring results of most organs in the chest and abdomen are good, and with slight modification, it can meet the clinical requirements for planning. With Atlas, auto-contouring results in most OAR is not as good as deep learning auto-segmentations, and only the auto-contouring results of some organs can be used clinically after modification.

Circular RNA THBS1 promotes proliferation and apoptosis of non-small cell lung cancer cells by sponging miR-129-5p and regulating SOX4 expression.

PURPOSE: To investigate the influence of circular ribonucleic acid thrombospondin-1 (circTHBS1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells by sponging miR-129-5p and regulating the expression of SRY-box transcription factor 4 (SOX4). METHODS: Carcinoma and para-carcinoma specimens were collected from 40 NSCLC patients, and 25 pairs of specimens were obtained from patients with metastatic and non-metastatic NSCLC. After NSCLC cells were cultured, the proliferation was detected via cell counting kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) assays, and the cell cycle and apoptosis rate were analyzed through flow cytometry. Finally, the action targets of circTHBS1 were determined using dual-luciferase reporter gene assay, and Western blotting assay was applied to measure the changes in protein levels. RESULTS: The expression of circTHBS1 was markedly higher in NSCLC patients than that in control group, and it was increased in patients with metastatic NSCLC compared with that in patients with non-metastatic NSCLC. Moreover, the proliferative ability of the cells was weakened notably after transfection with small interfering (Si)-CircTHBS1, but it was enhanced remarkably after transfection with CircTHBS1-overexpression vector (OE). There were complementary sites in circTHBS1 for the 3'-UTR of miR-129-5p, and the fluorescence intensity of wild-type circTHBS1 declined evidently after interacting with miR-129-5p. Besides, there was a putative binding site between miR-129-5p and SOX4, and SOX4 expression was decreased obviously after overexpressing miR-129-5p but increased following overexpression of circTHBS1. CONCLUSIONS: CircTHBS1 promotes the proliferation and inhibits the apoptosis of NSCLC cells through targeting miR-129-5p and regulating SOX4 expression.

Note: a real-time beam current density meter.

We have developed a real-time beam current density meter for charged particle beams. It measures the mean current density by collimating a uniform and large diameter primary beam. The suppression of the secondary electrons and the deflection of the beam were simulated, and it was tested with a 105 keV Ar(7+) ion beam.