Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.

Objective:To establish and validate a clinical and CT radiomics combined model for predicting lymph node metastasis (LNM) risk in patients with hilar cholangiocarcinoma (HCCA).Methods:This was a case-control study. Data from 158 pathologically confirmed HCCA patients between January 2016 and January 2022 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Using stratified random sampling, the patients were randomly divided into a training set ( n=95) and an internal validation set ( n=63) at a 6∶4 ratio. According to postoperative pathology, 31 LNM-positive cases and 64 LNM-negative cases were in the training set, and 22 LNM-positive cases and 41 LNM-negative cases were in the internal validation set. A cohort of 50 HCCA patients was retrospectively collected from West China Hospital of Sichuan University between October 2018 and June 2021 as an external validation set, including 21 LNM-positive and 29 LNM-negative cases. Clinical features were selected by multivariate logistic regression analysis to establish a clinical model. Radiomics features were extracted from portal venous phase CT images using 3D Slicer software. A radiomics model was developed using the least absolute shrinkage and selection operator regression algorithm. A clinical-radiomics model was constructed by integrating clinical features and Radscore, and a nomogram was developed. The prediction performance of models was evaluated by the area under the receiver operating characteristic curve (AUC). The AUC values were compared using the DeLong test. Calibration curves and decision curves were plotted to assess calibration and clinical net benefit. Results:Clinical N (cN) staging was an independent risk factor for LNM ( OR=6.86, 95% CI 2.70-18.49, P<0.001). Totally 12 optimal features were selected to construct the radiomics model, and the clinical-radiomics nomogram model was constructed by combining cN staging and Radscore. In the external validation set, the AUC (95% CI) of the clinical model, radiomics model, and clinical-radiomics nomogram were 0.706 (0.576-0.836), 0.768 (0.637-0.899), and 0.803 (0.680-0.926), respectively. The nomogram achieved higher AUC than clinical and radiomics models with statistical significance ( Z=2.01, 2.21; P=0.044, 0.027). The calibration and decision curves demonstrated good model fit, providing clinical net benefits for patients. Conclusion:The clinical-radiomics nomogram model combining cN staging and CT radiomics features can effectively predict LNM risk in HCCA patients.

Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.

Objective To observe the reproducibility of radiomics feature(RF)extracted from virtual monoenergetic image(VMI)of rabbit VX2 hepatoma models obtained with 3 different dual-energy CT(DECT)systems,and to explore relationship of reproducibility and diagnostic performance of RF.Methods Fifteen rabbits with VX2 hepatoma were randomly divided into 3 groups(each n=5).Contrast-enhanced abdominal CT scanning under volume CT dose index(CTDIvol)levels of 6,9 and 12 mGy were performed with dual-source DECT(dsDECT),rapid kV switching DECT(rsDECT)and dual-layer detector DECT(dlDECT),respectively.VMI were reconstructed at 10 keV increments from 40 to 140 keV.RF were extracted from VMI,the reproducibility was assessed using intra-class correlation coefficient(ICC),and those with ICC≥0.8 were considered as reproducible RF.The percentage of reproducible features(denoted by R)were compared among different scanner pairings and different CTDIvol levels.Within each CTDIvol group,the reconstruction energy levels yielding the maximum number(denoted by N)of common RF across different scanner pairings were identified.The receiver operating characteristic(ROC)curve was drawn,the area under the curve(AUC)was calculated,and the diagnostic efficacies of reproducible RF and other RF were compared under optimal reproducible conditions.Spearman correlation coefficient between ICC and the corresponding AUC of RF were calculated.Results RrsDECT-dsDECT(6.45％,95％CI[2.36％,8.87％])was higher than RdlDECT-dsDECT(0.72％,95％CI[0.15％,1.79％])and RrsDECT-dlDECT(1.43％,95％CI[0.60％,4.06％])(all adjusted P＜0.05),R9mGy(3.70％,95％CI[1.31％,5.73％])and R12mGy(2.63％,95％CI[0.60％,6.69％])were higher than R6mGy(1.31％,95％CI[0.12％,1.55％])(all adjusted P＜0.05).The optimal reproducible reconstruction energy levels of RF under CTDIvol of 6,9 and 12 mGy concentrated at 50-70 keV.AUC of reproducible RFs were higher than of other RF(all adjusted P＜0.05)and had certain correlation with the reproducibility(rs=0.102-0.516,P＜0.05).Conclusion The reproducibility of RF extracted from contrast-enhanced VMI CT images of rabbit VX2 hepatoma models associated with DECT scanner,CTDIvol level and reconstruction energy level.RF with higher reproducibility might have better diagnostic performance.

Objective To investigate the value of CT radiomics combined with CT and preoperative pathological features for predicting postoperative early recurrence(ER)of local advanced esophageal squamous cell carcinoma(LAESCC).Methods Data of 334 patients with LAESCC were retrospectively analyzed.The patients were divided into training set(n=234)and verification set(n=100)at the ratio of 7:3 and were followed up to observe ER(recurrence within 12 months after surgery)or not.Univariate and multivariate logistic regression were used to analyze clinical,CT and preoperative pathological features of LAESCC in patients with or without ER in training set.The independent risk factors of ER were screened,and a CT-preoperative pathology model was constructed.Based on venous phase CT in training set,the radiomics features of lesions were extracted and screened to establish radiomics model,and finally a combined model was established based on radiomics model and the independent risk factors.Receiver operating characteristic(ROC)curves were drawn,and the area under the curve(AUC)was calculated to evaluate the diagnostic efficacy of each model.Results Among 334 cases,168 were found with but 166 without ER.In training set,117 cases were found with while the rest 117 without ER,while in verification set,51 were found with but 49 without ER.The length of lesions,cT stage and cN stage shown on CT and tumor differentiation degree displayed with preoperative pathology were all independent risk factors for ER of LAESCC(all P＜0.05).The AUC of CT-preoperative pathology model in training set and validation set was 0.759 and 0.783,respectively.Ten best radiomics features of LAESCC were selected,and AUC of the established radiomics model in training set and validation set was 0.770 and 0.730,respectively.The AUC of combined model in training and validation set was 0.838 and 0.826,respectively.The AUC of CT radiomics combined with CT and preoperative pathological features in training set was higher than that of CT-preoperative pathologymodel and radiomics model(both P＜0.01).Conclusion CT radiomics combined with CT and preoperative pathological features could effectively predict postoperative ER of LAESCC.

Objective To observe the value of clinical data combined with CT radiomics features for evaluating programmed cell death-ligand 1(PD-L1)status in gastric cancer.Methods Totally 277 gastric cancer patients were retrospectively enrolled and randomly divided into training set(n=195)and validation set(n=82)at the ratio of 7:3.There were 88 cases in PD-L1 positive subgroup and 107 cases in negative subgroup of training set,while 37 and 45 cases of validation set,respectively.The clinical and conventional CT features were compared between subgroups in both sets,the independent influencing factors of PD-L1 status in gastric cancer were analyzed,and radiomic features were screened based on CT data.Then clinical model,radiomics model and clinical-radiomics model were established,and the efficacy of each model for evaluating PD-L1 status in gastric cancer was observed.Results In training set,Borrmann type,cN stage,cM stage,clinical stage,maximum diameter and thickness were significant difference between subgroups(all P＜0.05).Borrmann type,clinical stage and the thickness were all independent influencing factors of PD-L1 positivity(all P＜0.05).The area under the curve(AUC)of clinical model,radiomic model and clinical-radiomics model for evaluating PD-L1 status in gastric cancer in training set was 0.748,0.832 and 0.841,respectively,and was 0.657,0.801 and 0.789 in validation set,respectively.AUC of clinical model was lower than the other models(all P＜0.05).Conclusion Clinical data combined with CT radiomics features was helpful for evaluating PD-L1 status in gastric cancer.

Objective:To investigate the value of CT quantitative parameters of tumor and spleen in predicting the clinical stage of gastric cancer (Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage).Methods:This study was a case-control study. The data of 145 patients with gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from February 2019 to June 2021 were retrospectively collected, including 70 cases of Ⅰ/Ⅱ stage and 75 cases of Ⅲ/Ⅳ stage. On the baseline CT images, the tumor related parameters, including tumor thickness, length of tumor, CT attenuation of tumor unenhanced phase, CT attenuation of tumor arterial phase, CT attenuation of tumor venous phase were measured. The spleen related parameters, including splenic thickness, CT attenuation of splenic unenhanced phase, CT attenuation of splenic arterial phase, CT attenuation of splenic venous phase, and standard deviation of CT attenuation (CTsd) in splenic unenhanced phase were also measured. The independent sample t test or Mann-Whitney U test was used to compare the parameters between the Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage patients. The multi-factor logistic regression analysis was used to find the independent predictors of gastric cancer clinical stage, and establish the combined parameters. The efficiency to the diagnosis of gastric cancer stage of single and combined parameters was evaluated using the operating characteristic curve, and the DeLong test was used to compare the differences of area under the curve (AUC). Results:There were significant differences in tumor thickness, length of tumor, CT attenuation of tumor venous phase, CT attenuation of splenic unenhanced phase, CT attenuation of splenic venous phase, CTsd in splenic unenhanced phase between the Ⅰ/Ⅱ stage and Ⅲ/Ⅳ stage of gastric cancer ( P<0.05). Multivariate analysis showed that tumor thickness ( OR=1.073, 95% CI 1.026-1.123, P=0.002), CT attenuation of splenic venous phase ( OR=1.040, 95% CI 1.011-1.070, P=0.006) and CTsd in splenic unenhanced phase ( OR=1.625, 95% CI 1.330-1.987, P<0.001) were independent risk factors for the clinical stage of gastric cancer and the combined parameters were established. The AUC values of tumor thickness, CT attenuation of splenic venous phase, CTsd in splenic unenhanced phase and combined parameters were 0.655, 0.614, 0.749 and 0.806, respectively. The AUC of combined parameters was higher than those of tumor thickness and CT attenuation of splenic venous phase, and the differences were statistically significant ( Z=3.37, 3.82, both P<0.001). Conclusion:Tumor thickness, CT attenuation of splenic venous phase and CTsd in splenic unenhanced phase are independent risk factors for the clinical stage of gastric cancer, and combined parameters can improve the diagnostic efficiency.

Objective:To investigate the predictive model construction of anastomotic thickening character after radical surgery of esophageal cancer based on computed tomogralphy(CT) radiomics and its application value.Methods:The retrospective cohort study was conducted. The clinicopathological data of 202 patients with esophageal squamous cell carcinoma (ESCC) who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2013 to June 2021 were collected. There were 147 males and 55 females, aged (63±8) years. Based on random number table, 202 patients were assigned into training dataset and validation dataset at a ratio of 7:3, including 141 cases and 61 cases respectively. Patients underwent radical resection of ESCC and enhanced CT examination. Observation indicators: (1) influencing factor analysis of malignant anas-tomotic thickening; (2) construction and evaluation of predictive model; (3) performance comparison of 3 predictive models. The normality of continuous variables was tested by Kolmogorov-Smirnov method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whintney U test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher's exact probability. The consistency between subjective CT features by two doctors and measured CT numeric variables was analyzed by Kappa test and intraclass correlation coefficient (ICC), with Kappa >0.6 and ICC >0.6 as good consistency. Univariate analysis was conducted by corresponding statistic methods. Multivariate analysis was conducted by Logistics stepwise regression model. The receiver operating characteristic (ROC) curve was drawn, and area under curve (AUC), Delong test, decision curve were used to evaluate the diagnostic efficiency and clinical applicability of model. Results:(1) Influencing factor analysis of malignant anastomotic thickening. Of the 202 ESCC patients, 97 cases had malignant anastomotic thickening and 105 cases had inflammatory anastomotic thickening. The consistency between subjective CT features by two doctors and measured CT numeric variables showed Kappa and ICC values >0.6. Results of multivariate analysis showed that the maximum thickness of anastomosis and CT enhancement pattern were independent influencing factors for malignant anastomotic thickening[ hazard ratio=1.46, 3.09, 95% confidence interval ( CI) as 1.26-1.71,1.18-8.12, P<0.05]. (2) Construction and evaluation of predictive model. ① Clinical predictive model. The maximum thickness of anasto-mosis and CT enhancement pattern were used to construct a clinical predictive model. ROC curve of the clinical predictive model showed an AUC, accuracy, sensitivity, specificity as 0.86 (95% CI as 0.80-0.92),0.77, 0.77, 0.80 for the training dataset, and 0.78 (95% CI as 0.65-0.89), 0.77, 0.77, 0.80 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset ( Z=1.22, P>0.05). ② Radiomics predictive model. A total of 854 radiomics features were extracted and 2 radiomics features (wavelet-LL_first order_ Maximum and original_shape_VoxelVolume) were finally screened out to construct a radiomics predictive model. ROC curve of the radiomics predictive model showed an AUC, accuracy, sensitivity, specificity as 0.87 (95% CI as 0.81-0.93), 0.80, 0.75, 0.86 for the training dataset, and 0.73 (95% CI as 0.63-0.83), 0.80, 0.76, 0.94 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset ( Z=-0.25, P>0.05). ③ Combined predictive model. Results of multivariate analysis and radiomics features were used to construct a combined predictive model. ROC curve of the combined predictive model showed an AUC, accuracy, sensitivity, specificity as 0.93 (95% CI as 0.89-0.97),0.84, 0.90, 0.84 for the training dataset, and 0.79 (95% CI as 0.70-0.88), 0.89, 0.86, 0.91 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset ( Z=0.22, P>0.05). (3) Performance comparison of 3 predictive models. Results of Hosmer-Lemeshow goodness-of-fit test showed that the clinical predictive model, radiomics predictive model and combined predictive model had a good fitting degree ( χ2=4.88, 7.95, 4.85, P>0.05). Delong test showed a significant difference in AUC between the combined predictive model and clinical predictive model, also between the combined predictive model and radiomics predictive model ( Z=2.88, 2.51, P<0.05 ). There was no significant difference in AUC between the clinical predictive model and radiomics predictive model ( Z=-0.32, P>0.05). The calibration curve showed a good predictive performance in the combined predictive model. The decision curve showed a higher distinguishing performance for anastomotic thickening character in the combined predictive model than in the clinical predictive model or radiomics predictive model. Conclusions:The maximum thickness of anastomosis and CT enhancement pattern are independent influencing factors for malignant anastomotic thickening. Radiomics predictive model can distinguish the benign from malignant thickening of anastomosis. Combined predictive model has the best diagnostic efficacy.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective:To investigate the efficiency of deep learning image reconstruction (DLIR) algorithm in the image quality and detection of hypovascular hepatic metastases under low radiation doses in comparison with adaptive statistical iterative construction-V (ASiR-V).Methods:Fifty-six patients with suspected hypovascular hepatic metastases who needed abdominal enhanced CT scans were collected prospectively in the First Affiliated Hospital of Zhengzhou University from January to April 2021. The patients received conventional radiation dose with tube current-time products of 400 mA CT scans in the first venous phase, low-dose CT scans in the second venous phase, which were set as tube current-time products of 280 mA for group A (19 cases), 200 mA for group B (19 cases) and 120 mA for group C (18 case), respectively. The images of first venous phase and 3 groups of second venous phase were both reconstructed with ASiR-V60% and high-DLIR (DLIR-H). Quantitative parameters [image noise, liver and portal vein signal to noise ratio (SNR), contrast to noise ratio (CNR)] and qualitative parameters (overall image quality, lesion conspicuity, diagnostic confidence) were compared between ASiR-V60% and DLIR-H images, and the effective radiation dose (ED) and the lesion detectability of each group was recorded. The paired t test was used to compare quantitative parameters, whereas the Wilcoxon signed-rank test of paired data was used to compare qualitative parameters. Results:In the second venous phase, ED was (5.56±0.35) mSv in group A, (3.88±0.23) mSv in group B, and (2.42±0.23) mSv in group C, with a decrease of 30%, 50% and 70% compared with the first venous phase, respectively. Moreover, with the decrease of radiation dose, the noise gradually increased, and the CNR lesions, SNR liver and SNR portal vein all gradually decreased. DLIR-H images had statistically better quantitative scores than ASiR-V60% images when the same radiation dose was applied (all P<0.001). Furthermore, the qualitative parameters of each group decreased with the decrease of radiation dose. Under the same radiation dose, the overall image quality, lesion conspicuity and diagnostic confidence of DLIR-H were higher than those of ASiR-V60% (all P<0.001). All lesions [100% (84/84)] were detected by ASIR-V60% and DLIR-H in group A, 92.0% (75/81) in group B, and 88.0% (79/89) in group C. Conclusions:Compared with ASiR-V60%, DLIR-H could reduce image noise, improve overall image quality and lesion conspicuity of hypovascular hepatic metastases as well as increase diagnostic confidence under different radiation doses.