Notes from the Field: Enhanced Surveillance for Raccoon Rabies Virus Variant and Vaccination of Wildlife for Management - Omaha, Nebraska, October 2023-July 2024.

On September 28, 2023, a kitten aged approximately 6 weeks found in Omaha, Nebraska, had test results positive for rabies at the Nebraska Veterinary Diagnostic Center (NVDC) after dying with neurologic signs and having bitten and scratched its caretakers. Preliminary investigation identified 10 exposed persons for whom postexposure prophylaxis (PEP)† was recommended. Subsequent variant-typing by NVDC yielded a presumptive positive result for the Eastern raccoon rabies virus variant (RRVV), which CDC confirmed on October 6.

Three-dimensional pseudo-continuous arterial spin-labelled perfusion imaging for diagnosing upper cervical lymph node metastasis in patients with nasopharyngeal carcinoma: a whole-node histogram analysis.

AIM: To evaluate whole-node histogram parameters of blood flow (BF) maps derived from three-dimensional pseudo-continuous arterial spin-labelled (3D pCASL) imaging in discriminating metastatic from benign upper cervical lymph nodes (UCLNs) for nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Eighty NPC patients with a total of 170 histologically confirmed UCLNs (67 benign and 103 metastatic) were included retrospectively. Pre-treatment 3D pCASL imaging was performed and whole-node histogram analysis was then applied. Histogram parameters and morphological features, such as minimum axis diameter (MinAD), maximum axis diameter (MaxAD), and location of UCLNs, were assessed and compared between benign and metastatic lesions. Predictors were identified and further applied to establish a combined model by multivariate logistic regression in predicting the probability of metastatic UCLNs. Receiver operating characteristic (ROC) curves were used to analyse the diagnostic performance. RESULTS: Metastatic UCLNs had larger MinAD and MinAD/MaxAD ratio, greater energy and entropy values, and higher incidence of level II (upper jugular group), but lower BF10th value than benign nodes (all p<0.05). MinAD, BF10th, energy, and entropy were validated as independent predictors in diagnosing metastatic UCLNs. The combined model yielded an area under the curve (AUC) of 0.932, accuracy of 84.42 %, sensitivity of 80.6 %, and specificity of 90.29 %. CONCLUSIONS: Whole-node histogram analysis on BF maps is a feasible tool to differentiate metastatic from benign UCLNs in NPC patients, and the combined model can further improve the diagnostic efficacy.

Prediction of programmed death-1 expression status in non-small cell lung cancer based on intratumoural and peritumoral computed tomography (CT) radiomics nomogram.

AIMS: This study aimed to predict the expression of programmed death-1 (PD-1) in non-small cell lung cancer (NSCLC) using intratumoral and peritumoral computed tomography (CT) radiomics nomogram. MATERIALS AND METHODS: Two hundred patients pathologically diagnosed with NSCLC from two hospitals were retrospectively analyzed. Of these, 159 NSCLC patients from our hospital were randomly divided into a training cohort (n=96) and an internal validation cohort (n=63) at a ratio of 6:4, while 41 NSCLC patients from another medical institution served as the external validation cohort. The radiomic features of the gross tumor volume (GTV) and peritumoral volume (PTV) were extracted from the CT images. Optimal radiomics features were selected using least absolute shrinkage and selection operator regression analysis. Finally, a CT radiomics nomogram of clinically independent predictors combined with the best rad-score was constructed. RESULTS: Compared with the 'GTV' and 'PTV' radiomics models, the combined 'GTV + PTV' radiomics model showed better predictive performance, and its area under the curve (AUC) values in the training, internal validation, and external validation cohorts were 0.90 (95% confidence interval [CI]: 0.83-0.97), 0.85 (95% CI: 0.74-0.96) and 0.78 (95% CI: 0.63-0.92). The nomogram constructed by the rad-score of the 'GTV + PTV' radiomics model combined with clinical independent predictors (prealbumin and monocyte) had the best performance, with AUC values in each cohort being 0.92 (95% CI: 0.85-0.98), 0.88 (95% CI: 0.78-0.97), and 0.80 (95% CI: 0.66-0.94), respectively. CONCLUSION: The intratumoral and peritumoral CT radiomics nomogram may facilitate individualized prediction of PD-1 expression status in patients with NSCLC.

Analysis of postoperative recurrence-free survival in non-small cell lung cancer patients based on consensus clustering.

AIMS: This study aims to assess whether consensus clustering, based on computed tomography (CT) radiomics from both intratumoral and peritumoral regions, can effectively stratify the risk of non-small cell lung cancer (NSCLC) patients and predict their postoperative recurrence-free survival (RFS). MATERIALS AND METHODS: A retrospective analysis was conducted on the data of surgical patients diagnosed with NSCLC between December 2014 and April 2020. After preprocessing CT images, radiomic features were extracted from a 9-mm region encompassing both the tumor and its peritumoral area. Consensus clustering was utilized to analyze the radiomics features and categorize patients into distinct clusters. A comparison of the differences in clinical pathological characteristics was conducted among the clusters. Kaplan-Meier survival analysis was employed to investigate differences in survival among the clusters. RESULTS: A total of 266 patients were included in this study, and consensus clustering identified three clusters (Cluster 1: n=111, Cluster 2: n=61, Cluster 3: n=94). Multiple clinical risk factors, including pathological TNM staging, programmed cell death ligand 1 (PD-L1), and epidermal growth factor receptor (EGFR) expression status exhibit significant differences among the three clusters. Kaplan-Meier survival analysis demonstrated significant variations in RFS across the clusters (P<0.001). The 3-year cumulative recurrence-free survival rates were 76.5% (95% CI: 68.6-84.4) for Cluster 1, 45.9% (95% CI: 33.4-58.4) for Cluster 2, and 41.5% (95% CI: 31.6-51.5) for Cluster 3. CONCLUSIONS: Consensus clustering of CT radiomics based on intratumoral and peritumoral regions can stratify the risk of postoperative recurrence in patients with NSCLC.

Predictive value of peritumour radiomics in the diagnosis of benign and malignant pulmonary nodules with halo sign.

AIM: To evaluate peritumour radiomics in predicting benign and malignant pulmonary nodules with halo sign. MATERIALS AND METHODS: In this retrospective study, 305 pulmonary nodules with halo sign (benign, 120; adenocarcinoma, 185) were collected. Manual segmentation was used to mark the gross tumour volume (GTV) and the peritumour volume (PTV) was established by uniform dilation (1 cm) of the tumour area in three dimensions. The GTV and PTV radiomic features were combined to produce the gross tumour and peritumour volume (GPTV). The minimum-redundancy maximum-relevance (mRMR) feature ranking method and least absolute shrinkage and selection operator (LASSO) algorithm were used to eliminate redundant radiomic features. Predictive models combined with clinical features and radiomic signatures were established. Multivarible logistic regression analysis was used to establish the combined model and develop a nomogram. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of the model. RESULTS: In the testing cohort, the area under the ROC curve (AUC) of the GTV, PTV, and GPTV radiomic models was 0.701 (95% CI: 0.589-0.814), 0.674 (95% CI: 0.557-0.791) and 0.755 (95% CI: 0.643-0.867), respectively. The AUC of the nomogram model based on clinical and GPTV radiomic signatures was 0.804 (95% CI: 0.707-0.901). CONCLUSION: The nomogram model based on clinical and GPTV radiomic signatures can better predict benign and malignant pulmonary nodules with halo signs, demonstrating that the model has potential as a convenient and effective auxiliary diagnostic tool for radiologists.

Radiomics nomogram integrating intratumoural and peritumoural features to predict lymph node metastasis and prognosis in clinical stage IA non-small cell lung cancer: a two-centre study.

AIM: To investigate the value of a radiomics nomogram integrating intratumoural and peritumoural features in predicting lymph node metastasis and overall survival (OS) in patients with clinical stage IA non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This study retrospectively enrolled 199 patients (training cohort: 71 patients from Affiliated Tumour Hospital of Nantong University; internal validation cohort: 46 patients from Affiliated Tumour Hospital of Nantong University; external validation cohort: 82 patients from the public database). CT radiomics models were constructed based on four volumes of interest: gross tumour volume (GTV), gross and 3 mm peritumoural volume (GPTV3), gross and 6 mm peritumoural volume (GPTV6), and gross and 9 mm peritumoural volume (GPTV9). The optimal radiomics signature was further combined with independent clinical predictors to develop a nomogram. Univariable and multivariable Cox regression analysis were applied to determine the relationship between factors and OS. RESULTS: GPTV6 radiomics yielded better performance than GTV, GPTV3, and, GPTV9 radiomics in the training (area under the curve [AUC], 0.81), internal validation (AUC, 0.79), and external validation cohorts (AUC, 0.71), respectively. The nomogram integrating GPTV6 radiomics and spiculation improved predictive ability, with AUCs of 0.85, 0.80, and 0.74 in three cohorts, respectively. Pathological lymph node metastasis, nomogram-predicted lymph node metastasis, and pleural indentation were independent risk predictors of OS (p<0.05). CONCLUSIONS: The nomogram integrating GPTV6 radiomics features and independent clinical predictors performed well in predicting lymph node metastasis and prognosis in patients with clinical stage IA NSCLC.

CT-based radiomics nomogram for the preoperative prediction of microsatellite instability and clinical outcomes in colorectal cancer: a multicentre study.

AIM: To develop and validate a computed tomography (CT)-based radiomics nomogram for preoperative prediction of microsatellite instability (MSI) status and clinical outcomes in colorectal cancer (CRC) patients. MATERIALS AND METHODS: This retrospective study enrolled 497 CRC patients from three centres. Least absolute shrinkage and selection operator regression was utilised for feature selection and constructing the radiomics signature. Univariate and multivariate logistic regression analyses were employed to identify significant clinical variables. The radiomics nomogram was constructed by integrating the radiomics signature and the identified clinical variables. The performance of the nomogram was evaluated through receiver operating characteristic curves, calibration curves, and decision curve analysis. Kaplan-Meier analysis was performed to investigate the prognostic value of the nomogram. RESULTS: The radiomics signature comprised 10 radiomics features associated with MSI status. The nomogram, integrating the radiomics signature and independent predictors (age, location, and thickness), demonstrated favourable calibration and discrimination, achieving areas under the receiver operating characteristic (ROC) curves (AUCs) of 0.89 (95% confidence interval [CI]: 0.83-0.95), 0.87 (95% CI: 0.79-0.95), 0.88 (95% CI: 0.81-0.96), and 0.86 (95% CI: 0.78-0.93) in the training cohort, internal validation cohort, and two external validation cohorts, respectively. The nomogram exhibited superior performance compared to the clinical model (p<0.05). Additionally, survival analysis demonstrated that the nomogram successfully stratified stage II CRC patients based on prognosis (hazard ratio [HR]: 0.357, p=0.022). CONCLUSION: The radiomics nomogram demonstrated promising performance in predicting MSI status and stratifying the prognosis of patients with CRC.

[Epidemiological characteristics of human adenovirus 2, 3 and 7 genetypes in hospitalized children with respiratory infection in a hospital of pediatric in Hebei Province from 2018 to 2020].

Objective: To investigate the epidemiological characteristics of human adenovirus (HADV) 2, 3 and 7 in hospitalized children with respiratory infection. Methods: A total of 25 686 children with respiratory infection hospitalized at Children's Hospital of Hebei Province from January 2018 to December 2020 were retrospectively included.Deep sputum or nasopharyngeal aspirates of those children were collected. Then thirteen common respiratory pathogens were detected by multiplex PCR. 510 HADV positive specimens were randomly selected via random number and classified for type 2, 3 and 7 using a multiplex real-time quantitative PCR. SPSS 21.0 software was used to perform all of the statistical analyses. Enumeration data were expressed by frequency and percentage. χ2 test was used for comparison between groups. Results: The HADV-positive rate was 7.99% (2 052/25 686). Children at age 3-<6 years had the highest HADV-positive rate (11.44%). The HADV-positive rate in 2019 was highest (10.64%). Among the 510 HADV-positive specimens, the proportion of type 3 was the highest (31.16%), followed by type 7 (21.37%) and type 2 (11.18%). The rate of type 2 in 2019 was significantly lower than that in 2018 and 2020 (χ2=8.954 and 16.354; P=0.003 and <0.01), while the rate of type 3 was significantly higher than that in 2018 and 2020 (χ2=5.248 and 4.811; P=0.022 and 0.028). The rate of type 2, type 3 and type 7 were lowest in winter, spring and autumn, respectively. The rate of type 2 increased significantly in autumn and the rate of type 3 and type 7 increased significantly in winter.The co-detection rate of HADV with other respiratory pathogens was 43.33%(221/510). Among, the co-detection rate of type 3 was highest (47.32%), and the co-detection rate of type 2, 3 and 7 was significantly higher than the alone detection rate (χ2=20.438, P<0.01; χ2=42.105, P<0.01; χ2=27.573, P<0.01).The proportion of severe pneumonia in children with type 7 positive (15.89%) was higher than that in children with non-type 7 positive (8.23%) (χ2=5.260, P=0.022). Conclusion: HADV is one of the important pathogens of children with respiratory infection in Children's Hospital of Hebei Province. The susceptible population of HADV is preschool children aged 3 to 6 years. HADV often co-detects with other respiratory pathogens. Type 3 and 7 is likely to be the dominant genotypes in this region, and type 7 may be one of the risk factors of severe pneumonia in children.

Preoperative prediction of the degree of differentiation of lung adenocarcinoma presenting as sub-solid or solid nodules with a radiomics nomogram.

AIM: To develop and validate a radiomics nomogram for prediction of degree of differentiation in lung adenocarcinoma presenting as sub-solid or solid nodules. MATERIALS AND METHODS: A total of 438 patients with histopathologically confirmed adenocarcinoma (248 non-poorly differentiated and 190 poorly differentiated) were divided into training cohort (n=235) and internal validation cohort (n=203) according to surgery sequence. Sixty patients form public TCIA dataset were selected for external validation. One thousand, two hundred and eighteen radiomics features were extracted from each volumetric region of interest and a least absolute shrinkage and selection operator logistic regression was applied to select meaningful radiomic features for building a radiomics score (Rad-score) model. A nomogram model incorporating the Rad-score and type was established after multivariable logistic regression. The discrimination efficiency, calibration efficacy, and clinical utility value of the nomogram were evaluated. RESULTS: The Rad-score model could predict the differentiation degree of lung adenocarcinoma with an area under the curve (AUC) of 0.83 (95% confidence interval [CI]: 0.78-0.89) in the internal validation cohort. The AUC of the nomogram and radiographic model was 0.86 (95% CI: 0.80-0.91), 0.78 (95% CI: 0.72-0.84) in the internal validation cohort respectively. The AUC of the nomogram in the external validation cohort was 0.73 (95% CI: 0.58-0.88). Delong's test showed that the nomogram performed better than radiographic features alone (p=0.001). CONCLUSIONS: The proposed radiomics nomogram has the potential to predict the differentiation degree of lung adenocarcinoma preoperatively.

[Clinical value of a differentiation prediction model for invasive lung adenocarcinoma].

Objective: To investigate the value of predicting the degree of differentiation of pulmonary invasive adenocarcinoma (IAC) based on CT image radiomics model and the expression difference of immunohistochemical factors between different degrees of differentiation of lesions. Methods: The clinicopathological data of patients with pulmonary IAC confirmed by surgical pathology in the Affiliated Huai'an First People's Hospital to Nanjing Medical University from December 2017 to September 2018 were collected. High-throughput feature acquisition was performed for all outlined regions of interest, and prediction models were constructed after dimensionality reduction by the minimum absolute shrinkage operator. Receiver operating characteristic curve was used to assess the predictive efficacy of clinical characteristic model, radiomics model and individualized prediction model combined with both to identify the degree of pulmonary IAC differentiation, and immunohistochemical expressions of Ki-67, NapsinA and TTF-1 were compared between groups with different degrees of IAC differentiation using rank sum test. Results: A total of 396 high-throughput features were extracted from all IAC lesions, and 10 features with high generalization ability and correlation with the degree of IAC differentiation were screened. The mean radiomics score of poorly differentiated IAC in the training group (1.206) was higher than that of patients with high and medium differentiation (0.969, P=0.001), and the mean radiomics score of poorly differentiated IAC in the test group (1.545) was higher than that of patients with high and medium differentiation (-0.815, P<0.001). The differences in gender (P<0.001), pleural stretch sign (P=0.005), and burr sign (P=0.033) were statistically significant between patients in the well and poorly differentiated IAC groups. Multifactorial logistic regression analysis showed that gender and pleural stretch sign were related to the degree of IAC differentiation (P<0.05). The clinical feature model consisted of age, gender, pleural stretch sign, burr sign, tumor vessel sign, and vacuolar sign, and the individualized prediction model consisted of gender, pleural stretch sign, and radiomic score, and was represented by a nomogram. The Akaike information standard values of the radiomics model, clinical feature model and individualized prediction model were 54.756, 82.214 and 53.282, respectively. The individualized prediction model was most effective in identifying the degree of differentiation of pulmonary IAC, and the area under the curves (AUC) of the individualized prediction model in the training group and the test group were 0.92 (95% CI: 0.86-0.99) and 0.88 (95% CI: 0.74-1.00, respectively). The AUCs of the radiomics group model for predicting the degree of differentiation of pulmonary IAC in the training group and the test group were 0.91 (95% CI: 0.83-0.98) and 0.87 (95% CI: 0.72-1.00), respectively. The AUCs of the clinical characteristics model for predicting the degree of differentiation of pulmonary IACs in the training and test groups were 0.75 (95% CI: 0.63-0.86) and 0.76 (95% CI: 0.59-0.94), respectively. The expression level of Ki-67 in poorly differentiated IAC was higher than that in well-differentiated IAC (P<0.001). The expression levels of NapsinA, TTF-1 in poorly differentiated IAC were higher than those in well-differentiated IAC (P<0.05). Conclusions: Individualized prediction model consisted of gender, pleural stretch sign and radiomics score can discriminate the differentiation degree of IAC with the best performance in comparison with clinical feature model and radiomics model. Ki-67, NapsinA and TTF-1 express differently in different degrees of differentiation of IAC.

Inhibitory effects of essential oils from Asteraceae plant against pathogenic fungi of Panax notoginseng.

AIMS: Diseases caused by pathogenic fungi was a major constrain in increasing productivity and improving quality of Panax notoginseng. The aim of this research was to evaluate the inhibitory activity of essential oils (EOs) from Asteraceae family, Chrysanthemum indicum and Laggera pterodonta, against pathogenic fungi of P. notoginseng. METHODS AND RESULTS: The antifungal activity was investigated using multiple methods, disclosing that the EOs from C. indicum and L. pterodonta are active against hypha growth of different fungi but with different degrees of potency. Checkerboard testing indicated that the combination of EOs with hymexazol had synergistic effect against Pythium aphanidermatum, and exhibited additive effects against bulk of targeted pathogenic fungi. Besides, we found that the baseline sensitivity of Fusarium oxysporum to L. pterodonta EOs was higher than those of C. indicum by means of mycelium growth rate method. Finally, the practicability of those EOs as plant pesticide was confirmed by in vivo model showing that EOs can significantly inhibit the occurrence of root rot of P. notoginseng caused by F. oxysporum. CONCLUSION: Those studies suggest that the EOs from C. indicum and L. pterodonta had the potential to develop into new pollution-free pesticides for the protection of precious Chinese herbal medicines. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided a new way of biological control for overcoming the frequent diseases occurrence of P. notoginseng.

A radiomics-based model to differentiate glioblastoma from solitary brain metastases.

AIM: To differentiate glioblastoma (GBM) from solitary brain metastases (MET) using radiomic analysis. MATERIALS AND METHODS: Two hundred and fifty-three patients with solitary brain tumours (157 GBM and 98 solitary brain MET) were split into a training cohort (n=178) and a validation cohort (n=77) by stratified sampling using computer-generated random numbers at a ratio of 7:3. After feature extraction, minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to build the radiomics signature on the training cohort and validation cohort. Performance was assessed by radiomics score (Rad-score), receiver operating characteristic (ROC) curve, calibration, and clinical usefulness. RESULTS: Eleven radiomic features were selected as significant features in the training cohort. The Rad-score was significantly associated with the differentiation between GBM and solitary brain MET (p<0.001) both in the training and validation cohorts. The radiomics signature yielded area under the curve (AUC) values of 0.82 and 0.81 in the training and validation cohorts to distinguish between GBM and solitary brain MET. CONCLUSIONS: The radiomics model might be a useful supporting tool for the preoperative differentiation of GBM from solitary brain MET, which could aid pretreatment decision-making.

[Intein-Mediated Protein trans-Splicing of the Recombinant Streptavidin on Magnetosomes].

When expressing streptavidin recombinant polypeptide on magnetosomes (called bacterial magnetic nanoparticles, or BMPs), the presence of endogenous bacterial biotin might be detrimental. In the study, the streptavidin monomer fragment (S1-116) was fused with the intein N-terminal (termed precursor S1-116-IN), and S1-116-IN was expressed in E. coli (BL21). Meanwhile, the SA117-160 fragment was fused with the C-terminal intein, and then this chimeric polypeptide was expressed on magnetosomes by fusion with magnetosome membrance protein MamF. In the in vitro protein splicing system, the purified engineered magnetosomes (BMP-SA117-160-IC) and the S1-116-IN precursor were mixed. Intein-mediated trans-splicing reaction was induced to produce the functional magnetic beads BMP-SA. Our results indicate that intein-mediated protein trans-splicing may lead to efficient synthesis of the recombinant streptavidin on the magnetosomes, showing its promising potential to produce other functional magnetic nanoparticles.

[Association of urinary sodium excretion with fluid overload in patients with chronic kidney disease].

Objective: To investigate the relationship between urinary sodium excretion and fluid overload (FO) in non-dialysis patients with chronic kidney disease (CKD). Methods: Patients with CKD stage 1-4 who underwent bioelectrical impedance (BIA) in the Department of Nephrology, Jiangsu Province Hospital from December 2019 to January 2021 were recruited. All enrolled patients were categorized into two groups according to whether or not they develop FO. Further, clinical parameters were compared between the two groups. Spearman correlation analysis was used to investigate the association between over hydration/extracellular water (OH/ECW) and clinical characteristics. Multivariate logistic regression analysis was performed to evaluate the relationship between urinary sodium excretion and FO (FO was defined as OH/ECW≥7%). Results: A total of 385 patients with CKD stage 1-4 were finally included in the study, with a mean age of (46±15) years. There were 216 male cases (56.1%), and 150 cases (39.0%) existed FO. Spearman correlation analysis indicated that OH/ECW positively correlated with urinary sodium excretion (r=0.147, P=0.004), urinary protein excretion (r=0.555, P<0.001) and systolic blood pressure (r=0.241, P<0.001), but inversely related to estimated glomerular filtration rate (eGFR) (r=-0.111, P=0.030) and serum albumin (r=-0.659, P<0.001). After adjusting for confounding factors including age, systolic blood pressure, diabetes, urinary protein excretion, serum albumin, serum sodium, serum chlorine, urinary calcium excretion, urinary phosphorus excretion and use of diuretics, multivariate logistic regression analysis demonstrated that higher level of urinary sodium excretion was associated with increased risk of FO in patients with CKD (OR=1.005, 95%CI: 1.000-1.011, P=0.048). Conclusion: High urinary sodium excretion is independently associated with fluid FO in non-dialysis patients with CKD.

[Analysis of epidemiological characteristics of human coronavirus in hospitalized children with respiratory tract infection in Hebei region].

Objective: To investigate the epidemiological characteristics of human coronavirus (HCoV) in hospitalized children with respiratory tract infection in Hebei region, providing evidence for the diagnosis and prevention of children with respiratory tract infection. Methods: A retrospective study was conducted on 1 062 HCoV positive children hospitalized for respiratory tract infection in Children's Hospital of Hebei Province from January 2015 to December 2020, aged from 33 days to 14 years, with a median age of 2 years. 27 932 (60.9%) were males and 17 944(39.1%) were females. And the gender, ages, seasonal distribution, HCoV-positive rates, co-detection distribution and clinical diagnosis of HCoV positive cases were analyzed by SPSS 25.0. Enumeration data were expressed by frequency and percentage; categorical variable were compared by the Pearson χ2test. Results: The overall HCoV-positive rate was 2.31% (1 062/45 876), which was 2.37% (662/27 932) in male children and 2.23% (400/17 944) in female children. There was no statistically significant difference between genders (χ²=0.916, P=0.339). Children at age groups<1 years (2.44%) and 1-<3 years (2.63%) had higher HCoV-positive rates than those at age groups 3-<5 years (1.97%) and ≥5 years (1.38%) (χ²=27.332,P<0.01). The HCoV-positive rates from 2015 to 2018 were 2.13%, 2.45%, 2.28% and 2.23%. The HCoV-positive rate of 2019 (1.71%) was significantly lower than in 2016 (χ²=12.05, P<0.01), 2017 (χ²=7.34, P=0.01) and 2018 (χ²=6.78, P=0.01), but there was no significant difference compared with 2015 (χ²=2.84, P=0.09). The HCoV-positive rate of 2020 (3.37%) was significantly higher than in 2015 (χ²=13.636, P<0.01), 2016 (χ²=11.099, P<0.01), 2017 (χ²=15.482, P<0.01), 2018(χ²=18.601, P<0.01) and 2019(χ²=45.580, P<0.01). The positive rate was highest in spring (March to May) in 2015 and 2017 to 2018. February to April and July to September of 2016 were the peak periods of positive detection. No obvious seasonal change was observed in 2019 and the HCoV-positive rate of 2020 was extremely low from January to July, following significantly increased from August to December. 26.37% (280/1 062) of HCoV were co-detected with other respiratory pathogens and the most frequently identified mixed detection was RSV. Three or more pathogens were detected in 7.34% (78/1 062) of the HCoV-positive samples. Bronchopneumonia and bronchiolitis were more frequently observed in the single HCoV positive (61.89% and 16.75%) children compared to co-detected children(34.29% and 9.64%)(χ²=63.394 and 8.228, P<0.01). However, compared to those with HCoV mono-detection, co-detected children were more likely to have severe pneumonia (4.6% and 47.14%) (χ²=280.171, P<0.01). Conclusions: HCoV is one of the respiratory pathogens in children in Hebei region and more prevalent in spring. The susceptible population of HCoV is mainly children under the age of 3 years old. HCoV often co-detects with other respiratory pathogens, and the co-infection is one of the risk factors of severe pneumonia in children with respiratory infection.

[Effect of tenofovir disoproxil fumarate antiviral therapy on virus-specific CD8+T Cells function in patients with chronic hepatitis B].

Objective: To observe the effect of tenofovir disoproxil fumarate (TDF) antiviral therapy on HBV-specific CD8(+)T cell function in peripheral blood of patients with HBeAg-positive chronic hepatitis B, and to assess its correlation with HBeAg sero-negativeness. Methods: Sixty-three cases with HLA-A02 restricted HBeAg-positive chronic hepatitis B who received TDF (300 mg/d) antiviral therapy were enrolled from October 2016 to July 2018. The peripheral blood CD8(+)T cells were separated at baseline and 48 weeks after treatment. The peripheral blood T cells count were detected by flow cytometry. The frequency of HBV-specific CD8(+)T cells secreting perforin, granzyme B, and interferon-γ (IFN-γ) were detected by enzyme-linked immunoblotting test. Direct and indirect contact co-culture system was established between HBV-specific CD8(+)T cells and HepG2.2.15 cells. HBV DNA was detected in the culture supernatant. Target cell mortality was calculated by lactate dehydrogenase level. Cytokines expression was detected by enzyme-linked immunosorbent assay. Virus-specific CD8(+)T cells cytokilling and non-cytokilling functions were evaluated. Measurement data of the two groups were compared by t-test or paired t-test. Results: Viral response, biochemical response, and HBeAg seroconversion rate at 48 weeks of TDF treatment were 100%, 90.48% (57/63), and 25.40% (16/63), respectively. There was no statistically significant difference in peripheral blood T cell count when compared with baseline and control group at 48 weeks of TDF treatment (P > 0.05). At 48 weeks of TDF treatment, the frequency of HBV-specific CD8(+)T cells secreting perforin, granzyme B, and IFN-γ in CHB patients was significantly higher than baseline (P < 0.001). Furthermore, the frequency of HBV-specific CD8(+)T cells secreting perforin, granzyme B, and IFN-γ was also significantly higher in CHB patients with HBeAg negative than that of non-negative (P < 0.05). HBV-specific CD8(+)T cells had induced significant down-regulation of HBV DNA in the supernatant of HepG2.2.15 cell culture (P < 0.001) and remarkable IFN-γ and interleukin-2 secretion (P < 0.05) at 48 weeks of TDF therapy in direct and indirect contact co-culture system. However, HepG2.2.15 cells death rate induced by virus-specific CD8(+)T cells was increased only in the direct contact co-culture system (21.7% ± 6.18% vs. 16.1% ± 4.15%, P < 0.001). Compared with HBeAg non-negative patients, HBeAg negative CHB patients with HBV-specific CD8(+)T cells had induced a strong decrease in HBV DNA (P < 0.001) and an increase in IFN-γ secretion level (P < 0.05). However, the target cell death proportion difference between HBeAg negative and non-negative patients was not statistically significant (P > 0.05). Conclusion: During TDF treatment, with the viral load reduction, virus-specific CD8(+)T cells cytokilling and non-cytokilling functions are significantly enhanced, and are closely related to HBeAg negative.

Effects of aging, baseline renal function and stage of HIV infection on post-treatment changes in renal function among HIV-infected patients: a retrospective cohort study.

OBJECTIVES: The use of combination antiretroviral therapy (cART) increases clinical uncertainty about changes in renal function. Specifically, little is known regarding the interaction of the effects of aging, baseline renal impairment, and stages of HIV infection on post-treatment changes in renal function. METHODS: This analysis included 5533 HIV-infected patients on cART in 2004-2016. Progression to chronic kidney disease (CKD) was defined as either two consecutive estimated glomerular filtration rate (eGFR) measurements < 60 mL/min/1.73 m2 for baseline eGFR ≥ 60 mL/min/1.73 m2 (mild renal impairment or normal renal function) or a 25% decline for baseline eGFR < 60 mL/min/1.73 m2 (moderate renal impairment). RESULTS: During follow-up (median 4.8 years), 130 (2.3%) of the patients progressed to CKD. A total of 20.1% of patients with baseline normal renal function progressed to mild renal impairment, while 74.0% of patients with baseline mild or moderate renal impairment improved to normal renal function. In multivariable analysis, a significant positive baseline-eGFR-by-World Health Organization (WHO)-stage interaction effect on progression to CKD in all patients was identified, indicating a cross-over effect from a reduced risk to an increased risk. A significant negative baseline-age-by-WHO-stage interaction effect on progression to mild renal impairment in patients with baseline normal renal function was identified, with adjusted hazard ratios progressively lower at older ages. In addition, there were significant associations with older age, lower baseline eGFR, Dai ethnic minority, and anaemia for both outcomes, hyperglycaemia for CKD only, and higher CD4 count, tenofovir and ritonavir-boosted lopinavir use for mild renal impairment only. CONCLUSIONS: Our data suggest a complex pattern of renal function dynamics in patients on cART, which requires precise management with systematic monitoring of the interaction of the effects of sociodemographic, nephrological and HIV-specific clinical characteristics.

Chemosensory proteins used as target for screening behaviourally active compounds in the rice pest Cnaphalocrocis medinalis (Lepidoptera: Pyralidae).

Reverse chemical ecology based on insect functional odorant binding proteins has been extensively studied to screen behaviourally active compounds, whereas chemosensory proteins (CSPs), which are reportedly involved in olfactory chemical reception and could serve as molecular targets remain unclear. In the present study, two behaviourally active compounds for Cnaphalocrocis medinalis, a serious pest of rice in Asia, were successfully screened via an antenna-biased CSP, CmedCSP33. Fluorescence competitive binding assays showed that CmedCSP33 could bind to seven out of 32 rice volatiles. Fluorescence quenching experiments revealed that CmedCSP33 forms a stable complex with nerolidol and ß-ionone, and circular dichroism (CD) spectra demonstrated that these two compounds cause conformational changes in CmedCSP33. Furthermore, H-tube olfactometer bioassays showed that C. medinalis displayed prominent attractant responses to nerolidol and prominent repellent responses to ß-ionone. Additionally, binding assays and CD spectra at different pH values implied that extensive conformational changes may be a general feature of CSPs for triggering the subsequent chemical transduction. Overall, our findings provide evidence for the involvement of CSPs in olfactory perception, and a protocol for effectively screening behaviourally active compounds.

A new reliable test for crossmatching: microplate hydrogel immunoassay technology.

OBJECTIVES: To provide a novel assay to detect incomplete antibodies in the crossmatching test. BACKGROUND: There is a requirement in China that both major and minor crossmatch tests are required. Among all methods of crossmatching, the tube anti-human globulin test requires tedious washing steps and is time-consuming, whereas the microcolumn gel immunoassay anti-human globulin test is susceptible to sample quality. METHODS: The process of the microplate hydrogel immunoassay anti-human globulin test involves the use of our patented hydrogel chromatography medium and U-bottom microplates pre-coated with goat anti-human globulin (AHG). A mixture of red blood cells (RBCs) and serum is centrifuged through the hydrogel under precise conditions. In incompatible reactions, the sensitised RBCs are captured by the pre-coated AHG and form a layer over the bottom of the well, whereas in compatible reactions, the unbound RBCs form a button at the bottom of the well. The sensitivity of this new approach and the performance when testing old specimens were evaluated. RESULTS: This approach was more convenient and slightly more sensitive than the tube anti-human globulin test and was superior to the microcolumn gel immunoassay when testing old specimens. CONCLUSION: In general, this assay is suitable for the routine clinical use of crossmatching to detect incomplete antibodies.

[Effects of titanium dioxide nanoparticles and lipopolysaccharide on antioxidant function of liver tissues in mice].

OBJECTIVE: To compare the effects of different sized titanium dioxide (titanium dioxide, TiO2) on the antioxidant function of liver tissues in mice, and study the effect of TiO2 nanoparticles on the susceptibility of lipopolysaccharide (LPS) on liver tissues. METHODS: Ninety 4-week-old clean-grade male ICR mice were divided into 18 groups, in which the mice were fed for different feed involving ordinary feed, nanometer TiO2 feed which meant the feed including 1% (mass fraction) TiO2 nanoparticles, and submicron TiO2 feed which meant the feed including 1% (mass fraction) TiO2 submicron particles. Respectively, they were fed for 1 month, 3 months and 6 months. On the second day after the feeding, respectively, 0 and 10 mg/kg LPS were given by gavage. The mice were harvested after 4 h and the body weight and liver weight for calculating the liver coefficient were recorded. Then the liver tissue homogenates were prepared for determining the antioxidant indexes including the total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA). RESULTS: The change of body weight in mice was only discovered in group fed for 1 month, which showed significant decrease of body weight in treatment groups compared with control group. And there was no significant change of the liver coefficient in each group. Compared with control groups, nanometer TiO2 groups and submicron TiO2 group, the activity of T-AOC, T-SOD and MDA of nanometer TiO2+LPS group and submicron TiO2+LPS group in which the mice were fed for 1 month and 6 months increased in different degree. And another result was also existing. The MDA activity of liver in different sized treatment groups fed for 3 months decreased. Neither significant difference between the results of different sized TiO2 treatment groups, nor significant difference among different sized TiO2 groups and the control groups were observed. CONCLUSION: Longterm peroral TiO2 nanoparticles and TiO2 submicron particles are more likely to cause damage to the liver in the growing mice, and the damage may be either reductive or oxidative. In addition, small sized TiO2 can increase the susceptibility of mice liver to LPS and the susceptibility will increase with the increase of exposure time.