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Abstract Tobacco exposure is known to be associated with a higher prevalence and incidence of liver diseases. Cotinine, a metabolite of nicotine, is a typical indicator of tobacco exposure. However, the relationship of serum cotinine levels with hepatic steatosis and liver fibrosis remains controversial and these relationships need more research to explored in American teenagers. Cross-sectional data included 1433 participants aged 12–19 from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020 were thoroughly used for this study. The linear relationships between serum cotinine levels and the Liver Stiffness Measurement (LSM) and Controlled Attenuation Parameter (CAP) were examined using multiple linear regression models. Subgroup analysis, interaction tests, and nonlinear interactions were also carried out. Serum cotinine levels > 2.99 ng/ml [β = 0.41 (0.07, 0.76), p = 0.018] and 0.05–2.99 ng/ml [β = 0.24 (0.00, 0.49), p = 0.048] showed a significant positive connection with LSM in multivariate linear regression analysis when compared to serum cotinine levels ≤ 0.05 ng/ml (p for trend = 0.006). Moreover, we discovered an inverted U-shaped association of log2-transformed cotinine with LSM with an inflection point of 4.53 using a two-stage linear regression model. However, according to multiple regression analysis, serum cotinine and CAP did not significantly correlate (p = 0.512). In conclusion, this study demonstrated that smoking cessation and keep away from secondhand smoking may beneficial for liver health in American teenagers.

Abstract Background The RNA profiles of tumor-educated platelets (TEPs) possess pathological features that could be used for early cancer detection. However, the utility of TEP RNA profiling in detecting early colorectal cancer (CRC) versus noncancerous colorectal diseases has not yet been investigated. This study assesses the diagnostic capacity of TEP RNA profiles in a cohort of patients with CRC and noncancerous diseases. Methods Transcriptome sequencing for platelets isolated from 132 patients with CRC at early and late stages and 190 controls consisting of healthy donors and patients with ulcerative disease, Crohn’s disease, polyps, and adenomas was performed and analyzed using binary particle swarm optimization coupled with support vector machine to identify genes that contributed to the classification of CRC patients versus controls. The area under the receiver operating curves (AUROCs) and the accuracy of TEP RNA profiles in CRC diagnosis were assessed. Results TEP RNA profiling achieved high performance in distinguishing and staging CRC patients from the controls. Using the swarm intelligence algorithm, the 921 most contributive genes that classified CRC patients from the controls were identified. AUROCs of 0.928 for the training set via leave-one-out cross-validation and 0.92 for the validation set were achieved, both of which were significantly higher than the clinically utilized serum biomarkers: carcinoembryonic antigen and cancer antigen 19-9. Notably, an AUROC of 0.915 in an external validation set was achieved. For predicting different CRC stages, an AUROC of 0.984 was achieved in the training set and 1.000 in the internal validation set. Conclusions RNA profiles of TEPs are of potential diagnostic value for identifying early CRC from noncancerous diseases. Prospective studies are needed to validate its clinical relevance.

Abstract The purpose of this study is to develop a nomogram model for early prediction of the severe mycoplasma pneumoniae pneumonia (SMPP) in Pediatric and Adult Patients. A retrospective analysis was conducted on patients with MPP, classifying them into SMPP and non-severe MPP (NSMPP) groups. A total of 550 patients (NSMPP 374 and SMPP 176) were enrolled in the study and allocated to training, validation cohorts. 278 patients (NSMPP 224 and SMPP 54) were retrospectively collected from two institutions and allocated to testing cohort. The risk factors for SMPP were identified using univariate analysis. For radiomic feature selection, Spearman’s correlation and the least absolute shrinkage and selection operator (LASSO) were utilized. Logistic regression was used to build different models, including clinical, imaging, radiomics, and integrated models (combining clinical, imaging, and radiomics features selected). The model’s discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer–Lemeshow goodness-of-fit test. Thirteen clinical features and fourteen imaging features were selected for constructing the clinical and imaging models. Simultaneously, a set of twenty-five radiomics features were utilized to build the radiomics model. The integrated model demonstrated good calibration and discrimination in the training cohorts (AUC, 0.922; 95% CI: 0.900, 0.942), validation cohorts (AUC, 0.879; 95% CI: 0.806, 0.920), and testing cohorts (AUC, 0.877; 95% CI: 0.836, 0.916). The discriminatory and predictive efficacy of the clinical model in testing cohorts increased further after clinical and radiological features were incorporated (AUC, 0.849 vs. 0.922, P = 0.002). The model demonstrated exemplary predictive efficacy for SMPP by leveraging a comprehensive set of inputs, encompassing clinical data, quantitative and qualitative radiological features, along with radiomics features. The integration of these three aspects in the predictive model further enhanced the performance of the clinical model, indicating the potential for extensive clinical applications.

Abstract Traditionally, the clinical evaluation of respiratory diseases was pulmonary function testing, which can be used for the detection of severity and prognosis through pulmonary function parameters. However, this method is limited by the complex process, which is impossible for patients to monitor daily. In order to evaluate pulmonary function parameters conveniently with less time and location restrictions, cough sound is the substitute parameter. In this paper, 371 cough sounds segments from 150 individuals were separated into 309 and 62 as the training and test samples. Short-time Fourier transform (STFT) was applied to transform cough sound into spectrogram, and ResNet50 model was used to extract 2048-dimensional features. Through support vector regression (SVR) model with biological attributes, the data were regressed with pulmonary function parameters, FEV1, FEV1%, FEV1/FVC, FVC, FVC%, and the performance of this models was evaluated with fivefold cross-validation. Combines with deep learning and machine learning technologies, the better results in the case of small samples were achieved. Using the coefficient of determination (R2), the ResNet50 + SVR model shows best performance in five basic pulmonary function parameters evaluation as FEV1(0.94), FEV1%(0.84), FEV1/FVC(0.68), FVC(0.92), and FVC%(0.72). This ResNet50 + SVR hybrid model shows excellent evaluation of pulmonary function parameters during coughing, making it possible to realize a simple and rapid evaluation for pneumonia patients. The technology implemented in this paper is beneficial in judge the patient's condition, realize early screening of respiratory diseases, evaluate postoperative disease changes and detect respiratory infectious diseases without time and location restrictions.

Objective To evaluate the necessity and rationality of setting 0.7 CO of the gray area of HBV surface antigen reagent (ELISA) in our laboratory, and to provide the basis for the grey area setting. Methods A total of 60 samples of serum plate were repeatability tested by two kinds of ELISA HBsAg reagents. Based on the test results, C50, C5, C95 concentrations and corresponding S / CO values were calculated, and whether C5 and C95 were within C50±20% was verified. At the same time, the true positive rate and the confirmed positive rate of gray area samples revealed by two reagents were calculated. Results The confirmation results of serum plate were as follows: The C50, C5 and C95 concentrations of reagent A were 0.090 IU/mL, 0.075 IU/mL, 0.105 IU/mL. The true positive rate was 99.1%(436/440), the confirmed positive rate of grey area was37.8%(136/360). The C50, C5 and C95 concentrations of reagent B were 0.112 IU/mL, 0.091 IU/mL, and 0.133 IU/mL; the true positive detection rate was 97.1%(233/240); the confirmed positive rate of grey area was 35.8%(129/360). It was verified that C5 and C95 of reagent A and reagent B were within their respective C50±20%, and the gray areas of the HBsAg ELISA were verified to be effective. Conclusion It is necessary to set the gray area for these two HBsAg ELISA reagents in our laboratory, but the gray area value setting to 0.7 CO is unreasonable. The best gray area value was 0.75 CO in reagent A and 0.63 CO in reagent B.

ObjectivesUnexplained recurrent spontaneous abortion (URSA) remains an intractable reproductive dilemma due to the lack of understanding of the pathogenesis. This study aimed to evaluate the preclinical evidence for the mesenchymal stromal cell (MSC) treatment for URSA.MethodsA meticulous literature search was independently performed by two authors across the Cochrane Library, EMBASE, and PubMed databases from inception to April 9, 2023. Each study incorporated was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. The amalgamated standardized mean difference (SMD) accompanied by 95% confidence interval (CI) were deduced through a fixed-effects or random-effects model analysis.ResultsA total of ten studies incorporating 140 mice were subjected to data analysis. The MSC treatment yielded a significant reduction in the abortion rate within the URSA model (OR = 0.23, 95%CI [0.17, 0.3], P0.05).ConclusionsThe findings underscore the considerable potential of MSCs in URSA therapy. Nonetheless, the demand for enhanced transparency in research design and direct comparisons between various MSC sources and administration routes in URSA is paramount to engendering robust evidence that could pave the way for successful clinical translation.

Enhancers are key transcriptional drivers of gene expression. The identification of enhancers in the genome is central for understanding gene-expression programs. Although transposon-mediated enhancer trapping (ET) is a powerful approach to the identification of enhancers in zebrafish, its efficiency varies considerably. To improve the ET efficiency, we constructed Tol2-mediated ET vectors with a reporter gene (mCherry) expression box driven by four minimal promoters (Gata, Myc, Krt4 and Oct4), respectively. The ET efficiency and expression background were compared among the four promoters by zebrafish embryo injection at the one-cell stage. The results showed that the Gata minimal promoter yielded the lowest basic expression and the second-highest trapping efficiency (44.6% at 12 hpf (hour post-fertilization) and 23.1% at 72 hpf, n = 305 and n = 307). The Krt4 promoter had the highest trapping efficiency (64% at 12 hpf and 67.1% at 72 hpf, n = 302 and n = 301) and the strongest basic expression. To detect enhancer activity, chicken 5′HS4 double insulators were cloned into the two ET vectors with the Gata or Krt4 minimal promoter, flanking the mCherry expression box. The resulting detection vectors were injected into zebrafish embryos. mCherry expression driven by the Gata promoter (about 5%, n = 301) was decreased significantly compared with that observed for embryos injected with the ET vectors (23% at 72 hpf, n = 308). These results suggest that the insulators block the genome-position effects and that this vector is fit for enhancer-activity evaluation. To assess the compatibility between the enhancers and the minimal promoters, four enhancers (CNS1, Z48, Hand2 and Hs769) were cloned upstream of the Gata or Beta-globin minimal promoter in the enhancer-activity-detection vectors. The resulting recombinant vectors were assayed by zebrafish embryo injection. We found that Z48 and CNS1 responded to the Gata minimal promoter, and that Hand2 only responded to the Beta-globin minimal promoter. In contrast, Hs769 did not respond to either the Gata or Beta-globin minimal promoters. These results suggest the existence of compatibility between enhancers and minimal promoters. This study represents a systematic approach to the discovery of optional ET and enhancer-detection vectors. We are eager to provide a superior tool for understanding functional genomics.

Effective and efficient spatial normalization of a large population of brain images is critical for many clinical and research studies, but it is technically very challenging. A commonly used approach is to choose a certain image as the template and then align all other images in the population to this template by applying pairwise registration. To avoid the potential bias induced by the inappropriate template selection, groupwise registration methods have been proposed to simultaneously register all images to a latent common space. However, current groupwise registration methods do not make full use of image distribution information for more accurate registration. In this paper, we present a novel groupwise registration method that harnesses the image distribution information by capturing the image distribution manifold using a hierarchical graph with its nodes representing the individual images. More specifically, a low-level graph describes the image distribution in each subgroup, and a high-level graph encodes the relationship between representative images of subgroups. Given the graph representation, we can register all images to the common space by dynamically shrinking the graph on the image manifold. The topology of the entire image distribution is always maintained during graph shrinkage. Evaluations on two datasets, one for 80 elderly individuals and one for 285 infants, indicate that our method can yield promising results.

The effect of time from diagnosis to treatment (TDT) on overall survival of patients with acute myeloid leukemia (AML) remains obscure. Furthermore, whether chemotherapy delay impacts overall survival (OS) of patients with a special molecular subtype has not been investigated. Here, we enrolled 364 cases of AML to assess the effect of TDT on OS by fractional polynomial regression in the context of clinical parameters and genes of FLT3ITD, NPM1, CEBPA, DNMT3a, and IDH1/2 mutations. Results of the current study show IDH1/2 mutations are associated with older age, M0 morphology, an intermediate cytogenetic risk group, and NPM1 mutations. TDT associates with OS for AML patients in a nonlinear pattern with a J shape. Moreover, adverse effect of delayed treatment on OS was observed in patients with IDH1/2 mutations, but not in those with IDH1/2 wildtype. Therefore, initiating chemotherapy as soon as possible after diagnosis might be a potential strategy to improve OS in AML patients with IDH1/2 mutations.

Since Feb, 2013, more than 100 human beings had been infected with novel H7N9 avian influenza virus. As of May 2013, several H7N9 viruses had been found in retail live bird markets (LBMs) in Guangdong province of southern China where several human cases were confirmed later. However, the real avian influenza virus infection status especially H7N9 in Guangzhou remains unclear. Therefore, a cross-sectional study of avian influenza in commercial poultry farms, the wholesale LBM and retail LBMs in one district of Guangzhou was conducted from October to November, 2013. A total of 1505 cloacal and environmental samples from 52 commercial poultry farms, 1 wholesale LBM and 18 retail LBMs were collected and detected using real-time RT-PCR for type A, H7, H7N9 and H9 subtype avian influenza virus, respectively. Of all the flocks randomly sampled, 6 farms, 12 vendors of the wholesale LBM and 18 retail LBMs were type A avian influenza virus positive with 0, 3 and 11 positive for H9, respectively. The pooled prevalence and individual prevalence of type A avian influenza virus were 33.9% and 7.9% which for H9 subtype was 7.6% and 1.6%, respectively. None was H7 and H7N9 subtype virus positive. Different prevalence and prevalence ratio were found in different poultry species with partridges having the highest prevalence for both type A and H9 subtype avian influenza virus. Our results suggest that LBM may have a higher risk for sustaining and transmission of avian influenza virus than commercial poultry farms. The present study also indicates that different species may play different roles in the evolution and transmission of avian influenza virus. Therefore, risk-based surveillance and management measures should be conducted in future in this area.

BACKGROUND:Anti-tuberculosis drug induced hepatotoxicity (ATDH) is a major adverse drug reaction associated for anti-tuberculosis therapy. The glutathione S-transferases (GST) plays a crucial role in the detoxification of hepatotoxic metabolites of anti-tuberculosis drugs.An association between GSTM1/GSTT1 null mutations and increased risk of ATDH has been demonstrated in adults. Given the ethnic differences and developmental changes, our study aims to investigate the potential impacts of GSTM1/GSTT1 genotypes on the development of ATDH in Han Chinese children treated with anti-tuberculosis therapy. METHODS:Children receiving anti-tuberculosis therapy with or without evidence of ATDH were considered as the cases or controls, respectively. The GSTM1 and GSTT1 genotyping were performed using the polymerase chain reaction. RESULTS:One hundred sixty-three children (20 cases and 143 controls) with a mean age of 4.7 years (range: 2 months-14.1 years) were included. For the GSTM1, 14 (70.0%) cases and 96 (67.1%) controls had homozygous null mutations. For the GSTT1, 13 (65.0%) cases and 97 (67.8%) controls had homozygous null mutations. Neither the GSTM1, nor the GSTT1 polymorphism was significantly correlated with the occurrence of ATHD. CONCLUSION:Our results did not support the GSTM1 and GSTT1 polymorphisms as the predictors of ADTH in Chinese Han children treated with anti-tuberculosis drugs. An age-related association between pharmacogenetics and ATHD need to be confirmed in the further study.

Yuanhu Zhitong Tablet (YZT) is an example of a typical and relatively simple clinical herb formula that is widely used in clinics. It is generally believed that YZT play a therapeutical effect in vivo by the synergism of multiple constituents. Thus, it is necessary to build the relationship between the absorbed fingerprints and bioactivity so as to ensure the quality, safety and efficacy. In this study, a new combinative method, an intestinal absorption test coupled with a vasorelaxation bioactivity experiment in vitro, was a simple, sensitive, and feasible technique to study on the absorbed fingerprint-efficacy of YZT based on chemical analysis, vasorelaxation evaluation and data mining. As part of this method, an everted intestinal sac method was performed to determine the intestinal absorption of YZT solutions. YZT were dissolved in solution (n = 12), and the portion of the solution that was absorbed into intestinal sacs was analyzed using rapid-resolution liquid chromatography coupled with quadruple time-of-flight mass spectrometry (RRLC-Q-TOF/MS). Semi-quantitative analysis indicated the presence of 34 compounds. The effect of the intestinally absorbed solution on vasorelaxation of rat aortic rings with endothelium attached was then evaluated in vitro. The results showed that samples grouped by HCA from chemical profiles have similar bioactivity while samples in different groups displayed very different. Moreover, it established a relationship between the absorbed fingerprints and their bioactivity to identify important components by grey relational analysis, which could predict bioactive values based on chemical profiles and provide an evidence for the quantification of multi-constituents.