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ObjectiveTo construct a Markov decision model for colorectal cancer screening, evaluate the long-term cost-effectiveness of different screening strategies, determine the optimal screening strategy, and provide a theoretical reference for improving colorectal cancer screening programs. MethodsA Markov decision model was constructed to simulate 25 screening strategies, including no screening, with screening start ages of 40, 45, and 50 years, end ages of 59, 64, 69, and 74 years, and screening intervals of 1 and 2 years. Data on the probabilities, screening costs, and medical costs required for the colorectal cancer natural history model were extracted from the Hubei Provincial Cancer Registration (2020)/Mortality Surveillance (2013 – 2017) dataset and the literature review and entered into the model. With a cycle length of 1 year, the health economic impact of different colorectal cancer screening strategies was predicted over multiple cycles. ResultsThe cost-effectiveness analysis at the individual level showed that the screening strategy with the lowest cost was 50-74-1 (annual primary screening with immunochemical fecal occult blood testing [iFOBT] and then required colonoscopy from 50 to 74 years of age), which cost 483 100 Chinese yuan (CNY) in social costs, gained 17.82 life-years (LY) and 16.76 quality-adjusted life-years (QALY), with a cost-effectiveness ratio (CER) of 27 100 CNY/LY and 28 800 CNY/QALY, using LY and QALY as outcome measures, respectively. The payback analysis showed that the 45-74-1 strategy (annual primary screening with iFOBT and then required colonoscopy from age 50 to 74 years) had the best cost-effectiveness ratio, consuming 515 200 CNY, gaining 19.49 LY and 18.37 QALY, with a CER of 26 400 yuan/LY and an incremental cost-effectiveness ratio (ICER) of 19 200 yuan/LY when using LY as the outcome measure, and a CER of 28 000 CNY/QALY and an ICER of 19 900 CNY/QALY when using QALY as the outcome measure. The strategy with the highest effect was 40-74-1 (annual screening from age 40 to 74), which cost 551 700 CNY in social costs and gained 20.97 LY and 19.78 QALYs, with a CER of 26 300 CNY/LY and an ICER of 24 700 CNY/LY using LY as the outcome measure, and a CER of 27 900 CNY/QALY and an ICER of 26 000 CNY/QALY using QALY as the outcome measure. The current colorectal cancer screening strategy in Wuhan, Hubei province, is 45-59-2 (biennial screening from age 45 to 59), which costs CNY 1 035 100 in social costs and gains 18.97 LY (16.8 QALY). The 45-74-1 strategy is more economical than the current strategy in Wuhan, saving 519 900 CNY and gaining an additional 0.52 LY (1.57 QALY). Considering the principle of maximum effect, the 40-74-1 screening strategy can save 483 400 CNY and gain an additional 2.00 LY (2.98 QALY) compared with the current colorectal cancer screening strategy in Wuhan. ConclusionUnder ideal economic conditions, the strategy (40-74-1) with the greatest effect can be prioritized; under limited economic resources, the screening strategy (45-74-1) with the best cost-effectiveness ratio can be prioritized.

Abstract Background Globally increasing atmospheric nitrogen (N) deposition has altered soil phosphorus (P) transformations and availability, and thereby influenced structure and function of terrestrial ecosystems. Edaphic characteristics and chemical form of deposited N could be important factors determining impacts of N deposition on soil P transformations, yet the underlying mechanisms remain largely unknown. Objectives of this study were to examine how mineral-N and amino N differently affect P fractions, and identify key soil properties determining N addition impacts on soil P transformations. Considering that amino N is an important component of deposited N and forest soils vary greatly in different regions, the results of present study can guide the management of forests across different soils under ongoing N deposition scenarios. Methods We conducted a 60-day laboratory experiment to investigate the effects of N addition (NH4NO3 and glycine) on soil P fractions and related biochemical properties in four representative forest soils (brown, yellow brown, aeolian sandy, and red soils) in China. Glycine and NH4NO3 were separately added at three rates (5, 10 and 20 g N m–2 yr–1). Results Firstly, the percent changes in organic P fractions with N addition were significantly greater than changes in inorganic P fractions across all soils. Secondly, the percent changes in P fractions with glycine and NH4NO3 additions were significantly correlated across all soils and treatments. However, glycine addition had significantly greater impacts on organic P fractions than NH4NO3 addition in the aeolian sandy and red soils with low organic carbon content. Thirdly, P fractions responded differently to N addition among the four soils. N-induced changes in microbial biomass and phosphatase activities, pH, exchangeable Ca2+ and Mg2+ contributed differently to the changes in P fractions with N addition in the four soils. Conclusions The different responses of P fractions to N addition in the four soils were mainly generated by the differences in extent of microbial N limitation, acid buffering capacity, and cation exchange capacity among the soils. The different impacts of mineral and amino N on soil P fractions can be ascribed to their divergent effects on soil pH, microbial biomass and activities.

The non-uniform suspended sediment flowing into the Yangtze River Estuary (YRE) has a substantial impact on riverbed evolution and the ecological environment. Conducting a numerical simulation can provide missing measurement data and act as an important support for river management. In this study, we developed a formula for determining the non-uniform suspended sediment-carrying capacity (SCC) based on the statistical theory of sediment transport. The formula was applied to a river network model domaining the tidal section of the lower reaches of the Yangtze River (LYR) to simulate the non-uniform suspended sediment flowing into the YRE. The verification results showed that the model accurately simulated fine-grained sediments with a high measurement accuracy. The simulation results for coarse-grained sediments were consistent with riverbed evolution that manifests as erosion. Owing to the sediment transport complexity in natural rivers, we propose a method for optimizing calculations of the SCC that provides more accurate modeling results and can be adapted when the observational measurement accuracy is improved in the future. These findings provide support for simulations and measurements of non-uniform suspended sediment transported in the LYR.

ObjectiveTo analyze the cost-effectiveness of a colorectal cancer screening program using fecal DNA testing as initial screening in Wuhan, Hubei province, and to provide evidence for colorectal cancer screening decision making. MethodsWe collected detection results of 101 217 individuals who participated in a colorectal cancer screening program using stool DNA-based SDC2/AHDFE1/PPP2R5C methylation test as initial screening from October 20, 2021 to December 31, 2022 in Wuhan city. Patient costs associated with colorectal cancer screening and treatment were estimated through on-site surveys of 998 colorectal cancer patients at three tertiary hospitals in Wuhan city and a literature review of cost-effectiveness analyses of colorectal cancer screening. In addition, a sensitivity analysis was conducted to assess colonoscopy compliance among screened individuals. ResultsOf the 101 217 individuals who received the non-invasive colorectal cancer gene test, 4 483 (4.43%) were diagnosed with positive colorectal lesions and 3 200 underwent colonoscopy, of which 2 345 (71.38%) were found to have abnormalities. The total cost of the colorectal cancer screening program with fecal DNA testing was 34.8043 million Chinese yuan, the estimated total benefit was 297.5828 million yuan, and the estimated net benefit was 262.7785 million yuan, yielding a cost-benefit ratio of 1 : 8.55 for this screening program. Sensitivity analysis suggested that increasing colonoscopy compliance to 80%, 90%, and 100% could increase the cost-effectiveness ratio to 1 : 9.15, 1 : 9.78, and 1 : 10.36, respectively. ConclusionThe colorectal cancer screening program using fecal DNA testing for initial screening in Wuhan city has a high cost-benefit ratio, with increased colonoscopy compliance likely to result in even greater economic benefits.

Abstract Rationale Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. Objectives To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. Methods We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data. Results Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota. Conclusions Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.

IntroductionAlthough acupuncture is recommended by chronic obstructive pulmonary disease (COPD) treatment guidelines owing to its effects on dyspnea, the underlying neurobiological mechanisms of these effects remain unclear. This study aims to evaluate the efficacy of acupuncture in patients with stable COPD and explore the possible involvement of specific brain regions.MethodsThis is a prospective, multicenter, single-blind, randomized controlled trial. A total of 90 participants will be recruited from three centers and will be randomly assigned in a 1:1 ratio to undergo acupuncture at acupoints on the disease-affected meridian (DAM) or non-acupoints on the non-affected meridian (NAM), in addition to routine pharmacological treatments. All participants will undergo 30 min of acupuncture three times a week for 8 weeks and will be followed up for 12 months. The primary outcome will be the severity of dyspnea, as measured using the Borg Dyspnea Scale and a visual analog scale at rest and after exercise. The secondary outcomes will include the multidimensional profile of dyspnea using Dyspnea-12, the modified Medical Research Council Dyspnea Scale, and the COPD assessment test; quality of life assessments using St George's Respiratory Questionnaire and the Hospital Anxiety and Depression Scale; and additional measurements of exacerbation frequency, pulmonary function, and the 6-min walking distance. Magnetic resonance imaging (MRI) will be performed before and after exercise to explore the potential neurobiological mechanisms of exertional dyspnea. Anxiety and depression will be measured and analyzed for their correlation with the activation of specific brain areas involved in dyspnea.DiscussionThis randomized controlled trial aims to use a multidimensional evaluation of the efficacy of acupuncture in relieving dyspnea in patients with COPD in terms of emotion and quality of life and explore the neurobiological mechanisms underlying the effects of acupuncture on dyspnea from an imaging perspective. It is expected to provide strong evidence to support the use of acupuncture in relieving dyspnea in patients with COPD and those with aother diseases involving dyspnea. Additionally, it provides novel insights into the central mechanisms of acupuncture intervention and dyspnea.Trial registrationChinese Clinical Trial Registry (https://www.chictr.org.cn/): ChiCTR2300071725.

Background: Dyspnea, a common symptom of chronic respiratory diseases (CRDs), is closely linked to higher levels of functional impairment and death, leading to significant societal and financial challenges. Despite numerous clinical trials and systematic reviews suggested the potential benefits of acupuncture for chronic obstructive pulmonary disease (COPD) and lung cancer, there is currently insufficient evidence to conclusively prove its effectiveness in alleviating dyspnea in patients with CRDs. Methods: To compile and evaluate the existing data on the effectiveness and safety of acupuncture for managing dyspnea in CRDs. Randomized controlled trials investigating acupuncture for the treatment of dyspnea in patients with CRDs, such as COPD, lung cancer, asthma, bronchiectasis, interstitial lung disease, chronic pulmonary heart disease and bronchitis, were searched and retrieved from five electronic databases in English or Chinese. Results: A total of 23 studies meeting the inclusion criteria were found in databases, covering various CRDs such as COPD, lung cancer, and asthma. A meta-analysis that compared acupuncture to a control group (which included no acupuncture and sham acupuncture) found significant advantages for acupuncture in reducing dyspnea severity (P = 0.0003), increasing 6MWD (P

ObjectiveTo develop a contrast-enhanced computed tomography (CECT) based radiomics model using machine learning method and assess its ability of preoperative prediction for the early recurrence of hepatocellular carcinoma (HCC).MethodsA total of 297 patients confirmed with HCC were assigned to the training dataset and test dataset based on the 8:2 ratio, and the follow-up period of the patients was from May 2012 to July 2017. The lesion sites were manually segmented using ITK-SNAP, and the pyradiomics platform was applied to extract radiomic features. We established the machine learning model to predict the early recurrence of HCC. The accuracy, AUC, standard deviation, specificity, and sensitivity were applied to evaluate the model performance.Results1,688 features were extracted from the arterial phase and venous phase images, respectively. When arterial phase and venous phase images were employed correlated with clinical factors to train a prediction model, it achieved the best performance (AUC with 95% CI 0.8300(0.7560-0.9040), sensitivity 89.45%, specificity 79.07%, accuracy 82.67%, p value 0.0064).ConclusionThe CECT-based radiomics may be helpful to non-invasively reveal the potential connection between CECT images and early recurrence of HCC. The combination of radiomics and clinical factors could boost model performance.

Objectives: With the characteristics of mindfulness and breathing techniques, Tai Chi has been recommended with therapeutic values in chronic obstructive pulmonary disease (COPD). However, its strengths as a complementary exercise for conventional pulmonary rehabilitation (PR) remain unclear. Design and setting: This single-blinded randomised controlled trial recruited patients with mild to severe stable COPD. Eligible participants were randomly assigned to the group with usual care (control), total body recumbent stepper (TBRS) exercise, Tai Chi (TC), or combined TBRS exercise and Tai Chi (TBRS-TC). Patients received a two-month hospital-based supervised exercise, followed by a ten-month community- or home-based rehabilitation program. Results: A total of 120 participants were recruited, and 102 were included in the per-protocol analysis. The mean changes in St George’s Respiratory Questionnaire (SGRQ) total score from baseline to the post-hospital exercise in the control group, TBRS group, TC group, and TBRS-TC group was 2.62 (95 % CI −8.99 to 8.99), −9.28 (95 % CI −13.96 to −4.60), −10.19 (95 % CI −13.72 to −6.67), and −16.75 (95 % CI −20.25 to −13.24), respectively, with a statistically significant difference between groups in favor of the TBRS-TC exercise (P

IntroductionObservational studies have reported the association between gut microbiota and the risk of lower respiratory tract infections (LRTIs). However, whether the association reflects a causal relationship remains obscure.MethodsA bidirectional twosample Mendelian randomization (MR) analysis was conducted by assessing genome-wide association study (GWAS) summary statistics for gut microbiota taxa and five common LRTIs. MR methods including inverse-variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode were used to analyze the causality. Gene pleiotropy was tested using MR-Egger regression and MR-PRESSO methods. Cochran’s Q test was used to check for heterogeneity. Leave-one-out analysis was used to assess the stability of effect sizes. Detected significant associations were validated by using an independent LRTI GWAS summary statistics dataset. An optional MR method of causal analysis using summary effect estimates (CAUSE) was further performed as a validation to avoid potential false-positive results.ResultsAccording to the MR-Egger estimates in forward MR analysis, a causal effect of gut Blautia on increased odds of bronchiectasis and pneumonia was suggested. MR-Egger regression pleiotropy intercept methods detected no significant horizontal pleiotropy between the instrumental variables of these associations. MR-PRESSO global test examined no potential horizontal pleiotropy. Cochran’s Q test showed that no heterogeneity biased the results. The leave-one-out sensitivity analyses suggested robust causality results. These associations with consistent effect direction were successfully replicated in IVW analysis by using the validation GWAS dataset. However, these evidence of causality did not survive after applying strict Bonferroni correction or CAUSE analysis. The reverse MR analysis failed to achieve consistent results in the effect of LRTIs on gut microbiota through comprehensive discovery and validation processes.DiscussionThis study established no strong causality between genetically predicted gut microbiome and the risk of lower respiratory tract infections. However, specific subtypes of microbial genera, such as Blautia, were identified as potential influencers and require further investigation, particularly at the species or strain levels.

Background: Binafuxi granules are a traditional Uighur medicine (TUM) for treating the common cold with fever. However, high-quality clinical studies supporting its efficacy and safety are lacking. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial, patients with common cold and fever were randomly assigned to a high-dose group, low-dose group, and placebo group in a 1:1:1 ratio. Outcomes were time to fever relief, time to fever clearance, proportion of afebrile patients, time to symptom disappearance, rate of symptom disappearance, effective rate, emergency drug usage and safety assessment. Results: A total of 235 patients were recruited. Of these, 234 were included in the full analysis set (FAS), and 217 were included in the per-protocol set (PPS). In the FAS analysis, the median time to fever relief was 6.00 h, 5.54 h and 10.65 h (P = 0.31) in the high-dose group, low-dose group and placebo group, respectively. The median time to fever clearance was 18.29 h, 20.08 h and 25.00 h (P = 0.0018), respectively, and the proportion of afebrile patients was 92.4%, 89.7% and 71.4% (P = 0.0002), respectively. There was a significant difference in the disappearance time and disappearance rate of all symptoms and of individual symptoms. No serious adverse events were found. Conclusions: Binafuxi granules can dose-dependently shorten the fever course and improve clinical symptoms in patients suffering from the common cold with fever. Trial Registration: This trial was registered at Chinese Clinical Trial Registry (ChiCTR-IIR-17013379).

Abstract. Background:. Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Methods:. Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. Results:. The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) (χ2 = 19.83, P

Abstract Background Approximately 5% of adults have an episode of acute bronchitis each year, accounting for more than 10 million medical visits yearly. The primary goal of treatment is reduction of symptoms. Currently, available medications are questionable in effectiveness and safety and are not recommended for routine use in clinical practice. Although Chinese herbal medicine has been widely used in the management of acute bronchitis in China, evidence-based data is lacking. This trial aims to evaluate the efficacy and safety of Tanreqing oral liquid in the treatment of acute bronchitis with phlegm-heat obstructing lungs syndrome. Methods/design This study is a prospective, multi-center, randomized, double-blinded, parallel-group, placebo-controlled trial. A total of 270 acute bronchitis adult patients with phlegm-heat obstructing lungs syndrome will be enrolled from outpatients and emergency departments at nine study centers across China. All included patients will be randomly allocated to receive Tanreqing oral liquid or placebo oral liquid, 20 mL three times daily for seven consecutive days. The primary outcome will be cough resolution rate. Secondary outcomes will include change of bronchitis symptoms scores from baseline to post-treatment, cough relief rate, time to cough resolution, time to cough relief, resolution rate of a single symptom, combination medicine use, change of traditional Chinese medicine syndrome score from baseline to post-treatment, and adverse events. Discussion This trial may provide an alternative treatment option for acute bronchitis patients, especially those in outpatients and emergency departments. It may also add evidence to Chinese herbal medicine for treating acute bronchitis. Trial registration Chinese Clinical Trial Registry ChiCTR2000040264 . Registered on 26 November 2020

Gallbladder cancer (GBC) is a highly malignant tumor with extremely poor prognosis. Previous studies have suggested that the carcinogenesis and progression of GBC is a multi-stage and multi-step process, but most of them focused on the genome changes. And a few studies just compared the transcriptome differences between tumor tissues and adjacent noncancerous tissues. The transcriptome changes, relating to every stage of GBC evolution, have rarely been studied. We selected three cases of normal gallbladder, four cases of gallbladder with chronic inflammation induced by gallstones, five cases of early GBC, and five cases of advanced GBC, using next-generation RNA sequencing to reveal the changes in mRNAs and lncRNAs expression during the evolution of GBC. In-depth analysis of the sequencing data indicated that transcriptome changes from normal gallbladder to gallbladder with chronic inflammation were distinctly related to inflammation, lipid metabolism, and sex hormone metabolism; transcriptome changes from gallbladder with chronic inflammation to early GBC were distinctly related to immune activities and connection between cells; and the transcriptome changes from early GBC to advanced GBC were distinctly related to transmembrane transport of substances and migration of cells. Expression profiles of mRNAs and lncRNAs change significantly during the evolution of GBC, in which lipid-based metabolic abnormalities play an important promotive role, inflammation and immune activities play a key role, and membrane proteins are very highlighted molecular changes.

Litter decomposition is the main process that affects nutrient cycling and carbon budgets in mixed forests. However, knowledge of the response of the soil microbial processes to the mixed-litter decomposition of fresh leaf, semi-decomposed leaf and fine root is limited. Thus, a laboratory microcosm experiment was performed to explore the mixed-litter effects of fresh leaf, semi-decomposed leaf and fine root on the soil enzyme activity and microbial community in an evergreen broadleaf karst forest in Southwest China. Fresh leaf litter, semi-decomposed litter and fine root in the Parakmeria nitida and Dayaoshania cotinifolia forests, which are unique protective species and dominant species in the evergreen broadleaf forest, were decomposed alone and in all possible combinations, respectively. Our results showed that the mass loss of fresh leaf litter in three mixed-litter treatment was significantly higher than that in two mixed-litter treatment in the P. nitida and D. cotinifolia forests. Mass loss of fine root in the single litter treatment was significantly lower in the P. nitida forest and higher in the D. cotinifolia forest compared to that in the other litter treatments. There were insignificant differences in the activities of β-glucosidase (BG) and leucine aminopeptidase (LAP) between control and mixed-litter treatment in the P. nitida forest and between control and single litter treatment in the D. cotinifolia forest. The N-acetyl-β-D-glucosaminidase (NAG) activity was significantly increased by the single litter decomposition of fresh leaf and fine root and three mixed-litter decomposition in the P. nitida and D. cotinifolia forests. The activity of acid phospomonoesterase (AP) in the decomposition of fresh leaf litter was lower in the P. nitida forest and higher in the D. cotinifolia forest compared to that in control. The most dominant soil bacteria were Proteobacteria in the P. nitida forest and were Actinobacteria and Proteobacteria in the D. cotinifolia forest. Shannon, Chao1, ACE and PD indexes in the mixed-litter decomposition of fresh leaf and semi-decomposition litter were higher than that in control in P. nitida forest. There were insignificant differences in observed species and indexes of Chao1, ACE and PD between litter treatments in the D. cotinifolia forest. Richness of mixed-litter significantly affected mass loss, soil enzyme activity and microbial diversity in the P. nitida forest. Litter N concentration and the presence of fresh leaf litter were significantly correlated with the mass loss and soil enzyme activity in the P. nitida and D. cotinifolia forests. These results indicated that the presence of fresh leaf litter showed a non-negligible influence on mixed-litter decomposition and soil enzyme activity, which might be partly explained by litter initial quality in the P. nitida and D. cotinifolia forests.

ObjectiveThe purpose of this study was to investigate the preoperative prediction of Cytokeratin (CK) 19 expression in patients with hepatocellular carcinoma (HCC) by machine learning-based ultrasomics.MethodsWe retrospectively analyzed 214 patients with pathologically confirmed HCC who received CK19 immunohistochemical staining. Through random stratified sampling (ratio, 8:2), patients from institutions I and II were divided into training dataset (n = 143) and test dataset (n = 36), and patients from institution III served as external validation dataset (n = 35). All gray-scale ultrasound images were preprocessed, and then the regions of interest were then manually segmented by two sonographers. A total of 1409 ultrasomics features were extracted from the original and derived images. Next, the intraclass correlation coefficient, variance threshold, mutual information, and embedded method were applied to feature dimension reduction. Finally, the clinical model, ultrasonics model, and combined model were constructed by eXtreme Gradient Boosting algorithm. Model performance was assessed by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy.ResultsA total of 12 ultrasomics signatures were used to construct the ultrasomics models. In addition, 21 clinical features were used to construct the clinical model, including gender, age, Child-Pugh classification, hepatitis B surface antigen/hepatitis C virus antibody (positive/negative), cirrhosis (yes/no), splenomegaly (yes/no), tumor location, tumor maximum diameter, tumor number, alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutamyl-transpeptidase, albumin, total bilirubin, conjugated bilirubin, creatinine, prothrombin time, fibrinogen, and international normalized ratio. The AUC of the ultrasomics model was 0.789 (0.621 – 0.907) and 0.787 (0.616 – 0.907) in the test and validation datasets, respectively. However, the performance of the combined model covering clinical features and ultrasomics signatures improved significantly. Additionally, the AUC (95% CI), sensitivity, specificity, and accuracy were 0.867 (0.712 – 0.957), 0.750, 0.875, 0.861, and 0.862 (0.703 – 0.955), 0.833, 0.862, and 0.857 in the test dataset and external validation dataset, respectively.ConclusionUltrasomics signatures could be used to predict the expression of CK19 in HCC patients. The combination of clinical features and ultrasomics signatures showed excellent effects, which significantly improved prediction accuracy and robustness.

Introduction Increasing numbers of patients with non-haematological diseases are infected with invasive pulmonary aspergillosis (IPA), with a high mortality reported which is mainly due to delayed diagnosis. The diagnostic capability of mycological tests for IPA including galactomannan test, (1,3)-β-D-glucan test, lateral flow assay, lateral flow device and PCR for the non-haematological patients remains unknown. This protocol aims to conduct a systematic review and meta-analysis of the diagnostic performance of mycological tests to facilitate the early diagnosis and treatments of IPA in non-haematological diseases.Methods and analysis Database including PubMed, CENTRAL and EMBASE will be searched from 2002 until the publication of results. Cohort or cross-sectional studies that assessing the diagnostic capability of mycological tests for IPA in patients with non-haematological diseases will be included. The true-positive, false-positive, true-negative and false-negative of each test will be extracted and pooled in bivariate random-effects model, by which the sensitivity and specificity will be calculated with 95% CI. The second outcomes will include positive (negative) likelihood ratio, area under the receiver operating characteristic curve and diagnostic OR will also be computed in the bivariate model. When applicable, subgroup analysis will be performed with several prespecified covariates to explore potential sources of heterogeneity. Factors that may impact the diagnostic effects of mycological tests will be examined by sensitivity analysis. The risk of bias will be appraised by the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2).Ethics and dissemination This protocol is not involved with ethics approval, and the results will be peer-reviewed and disseminated on a recognised journal.PROSPERO registration number CRD42021241820.

The non-uniform suspended sediment flowing into the Yangtze River Estuary (YRE) has a substantial impact on riverbed evolution and the ecological environment. Conducting a numerical simulation can provide missing measurement data and act as an important support for river management. In this study, we developed a formula for determining the non-uniform suspended sediment-carrying capacity (SCC) based on the statistical theory of sediment transport. The formula was applied to a river network model domaining the tidal section of the lower reaches of the Yangtze River (LYR) to simulate the non-uniform suspended sediment flowing into the YRE. The verification results showed that the model accurately simulated fine-grained sediments with a high measurement accuracy. The simulation results for coarsegrained sediments were consistent with riverbed evolution thatmanifests as erosion. Owing to the sediment transport complexity in natural rivers, we propose a method for optimizing calculations of the SCC that providesmore accuratemodeling results and can be adapted when the observational measurement accuracy is improved in the future. These findings provide support for simulations and measurements of non-uniform suspended sediment transported in the LYR. [ABSTRACT FROM AUTHOR]