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Background: Up to 17% of cancer survivors have been reported to develop second primary cancers (SPC), which cause significant physical and economic distress and often complicate clinical decision-making. However, understanding of SPC remains limited and superficial. Human leukocyte antigen (HLA) is characterized by its polymorphism and has been associated with various diseases. This study aims to explore the role of HLA diversity in SPC incidence., Methods: We analyzed a cohort of 47,550 cancer patients from the UK Biobank. SNP-derived HLA alleles were used and SPC-related HLA alleles were identified using logistic regression, followed by stepwise filtering based on the Akaike information criterion (AIC) and permutation tests. Additionally, we examined the association between extragenetic factors and the risk of SPC in patients carrying hazardous HLA alleles., Results: During a median follow-up of 3.11 years, a total of 2894 (6.09%) participants developed SPC. We identified three protective HLA alleles (DRB1*04:03 and DPA1*02:02 for males and DRB5*01:01 for females) and two hazardous alleles (A*26:01 for males and DPB1*11:01 for females) about SPC. The presence of the protective alleles was associated with a reduced SPC risk (males: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.59-0.89; females: HR 0.81, 95% CI 0.70-0.93), while the hazardous alleles were linked to an increased risk (males: HR 1.27, 95% CI 1.03-1.56; females: HR 1.35, 95% CI 1.07-1.70). The hazardous allele A*26:01 indicated skin-lung organ-specific SPC occurrence in males. Animal fat and vitamin C were associated with SPC risk in males carrying the hazardous alleles, while free sugar and vegetable fat were linked to SPC risk in females., Conclusions: These results suggest that HLA alleles may serve as biomarkers for the susceptibility and organ-specific occurrence of SPC, while dietary modulation may mitigate hazardous alleles-related SPC risk, potentially aiding in the early prediction and prevention of SPC., (© 2024. The Author(s).)

Introduction: Precise staging and classification of liver fibrosis are crucial for the hierarchy management of patients. The roles of lactylation are newly found in the progression of liver fibrosis. This study is committed to investigating the signature genes with histone lactylation and their connection with immune infiltration among liver fibrosis with different phenotypes., Methods: Firstly, a total of 629 upregulated and 261 downregulated genes were screened out of 3 datasets of patients with liver fibrosis from the GEO database and functional analysis confirmed that these differentially expressed genes (DEGs) participated profoundly in fibrosis-related processes. After intersecting with previously reported lactylation-related genes, 12 DEGs related to histone lactylation were found and narrowed down to 6 core genes using R algorithms, namely S100A6, HMGN4, IFI16, LDHB, S100A4, and VIM. The core DEGs were incorporated into the Least absolute shrinkage and selection operator (LASSO) model to test their power to distinguish the fibrotic stage., Results: Advanced fibrosis presented a pattern of immune infiltration different from mild fibrosis, and the core DEGs were significantly correlated with immunocytes. Gene set and enrichment analysis (GSEA) results revealed that core DEGs were closely linked to immune response and chemokine signaling. Samples were classified into 3 clusters using the LASSO model, followed by gene set variation analysis (GSVA), which indicated that liver fibrosis can be divided into status featuring lipid metabolism reprogramming, immunity immersing, and intermediate of both. The regulatory networks of the core genes shared several transcription factors, and certain core DEGs also presented dysregulation in other liver fibrosis and idiopathic pulmonary fibrosis (IPF) cohorts, indicating that lactylation may exert comparable functions in various fibrotic pathology. Lastly, core DEGs also exhibited upregulation in HCC., Discussion: Lactylation extensively participates in the pathological progression and immune infiltration of fibrosis. Lactylation and related immune infiltration could be a worthy focus for the investigation of HCC developed from liver fibrosis., Competing Interests: Author W-wL was employed by the company Guangzhou Wondfo Health Science and Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Li, Xiao and Lai.)

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17-1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38-1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59-1.74, p < 0.001). The results of prospective analyses were similar. Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Li, Li, Hong, Cui, Zhang, Li, Xiao, Zhu, Zeng, Xu, Lai and Liu.)

Immune checkpoint inhibitors (ICIs) are safe and efficacious treatments for advanced primary liver cancer (PLC). The efficacy of different ICIs in the treatment of liver cancer remains unclear. The purpose of this study was to explore whether there is a difference in the efficacy and safety of various programmed cell death protein 1 (PD-1) inhibitors in combination with lenvatinib in the treatment of unresectable PLC. Patients with PLC treated with lenvatinib in combination with PD-1 inhibitors (camrelizumab, tislelizumab, sintilimab, or pembrolizumab) between January 2018 and December 2021 were retrospectively enrolled. Tumor response, adverse events, and grades were evaluated. Kaplan-Meier analysis and log-rank test were used to compare the overall survival and progression-free survival of patients treated with different PD-1 inhibitors. Cox regression analysis was used for univariate and multivariate analyses to identify clinical variables related to treatment efficacy. This study included a total of 176 patients who received a combination of lenvatinib and PD-1 inhibitors. Of these, 103 patients received camrelizumab, 44 received tislelizumab, 20 received sintilimab, and 9 received pembrolizumab. There was no significant difference in the pairwise comparison of camrelizumab, tislelizumab, sintilimab, and pembrolizumab using Kaplan-Meier survival analysis. Adverse events occurred in 40 (22.7%) patients (grade ≥ 3, 2.3%). The incidence of grade 3 adverse events among the four PD-1 inhibitor groups was below 5%. Camrelizumab, tislelizumab, sintilimab, and pembrolizumab are viable options for patients with unresectable PLC. These PD-1 inhibitors in combination with lenvatinib showed good safety profiles. The results guide selecting treatment for patients with unresectable PLC., (© 2023. The Author(s).)

The purpose of this study was to analyse the clinical characteristics of patients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) PCR re-positivity after recovering from coronavirus disease 2019 (COVID-19). Patients ( n = 1391) from Guangzhou, China, who had recovered from COVID-19 were recruited between 7 September 2021 and 11 March 2022. Data on epidemiology, symptoms, laboratory test results and treatment were analysed. In this study, 42.7% of recovered patients had re-positive result. Most re-positive patients were asymptomatic, did not have severe comorbidities, and were not contagious. The re-positivity rate was 39%, 46%, 11% and 25% in patients who had received inactivated, mRNA, adenovirus vector and recombinant subunit vaccines, respectively. Seven independent risk factors for testing re-positive were identified, and a predictive model was constructed using these variables. The predictors of re-positivity were COVID-19 vaccination status, previous SARs-CoV-12 infection prior to the most recent episode, renal function, SARS-CoV-2 IgG and IgM antibody levels and white blood cell count. The predictive model could benefit the control of the spread of COVID-19.

Background: Immune checkpoint inhibitors (ICIs) have improved survival outcomes and resulted in long-term responses in primary liver cancer in some patients. Nevertheless, not all patients with PLC could benefit from immunotherapy. Therefore, it is necessary to identify patients suitable for such therapy., Methods: 215 patients with primary liver cancer with immunotherapy from Nanfang Hospital were screened between August 2018 and October 2020 as a training set and our validation set included 71 patients of hepatocellular carcinoma from Jiangxi Cancer Hospital from May 2019 to July 2021. The primary endpoint was the disease control rate (DCR), and the secondary endpoints were overall survival (OS) and progression-free survival., Results: In the training set, neutrophil-lymphocyte ratio (NLR) ≥3 and alpha-fetoprotein (AFP) level ≥20 ng/mL were independently associated with non-DCR in the training set after adjusting for distant metastasis at baseline and targeted therapy combination. Furthermore, a hepatic immune predictive index (HIPI) based on NLR and AFP level was developed and patients with poor HIPI associated with worse clinical outcomes. In validation set, high HIPI was associated with poor OS., Conclusion: HIPI, based on NLR and AFP level, is an effective indicator in ICI-treated patients with primary liver cancer. Our findings may help guide the selection and on-treatment strategies for immunotherapies for primary liver cancer patients., (© 2022 S. Karger AG, Basel.)

Background & Aims: Immune checkpoint inhibitors (ICIs) play an increasingly important role in the treatment of primary liver cancer (PLC). Some patients with PLC experience symptoms of splenomegaly. Splenomegaly may affect the efficacy of ICIs due to an imbalance of the immune microenvironment. Currently, there is a lack of evidence on the relationship between splenomegaly and prognosis in patients with PLC treated with ICIs. This study analyzed the relationship between splenomegaly and prognosis in patients with PLC treated with ICIs., Methods: In this retrospective cohort study of 161 patients with PLC treated with ICIs, splenomegaly was diagnosed using computed tomography or magnetic resonance imaging and the impact of splenomegaly on patient survival was analyzed., Results: Through univariate and multivariate Cox regression analyses, we determined that splenomegaly was associated with shortened overall survival (p = 0.002) and progression-free survival (p = 0.013) in patients with PLC treated with ICIs. Kaplan-Meier analysis further validated our results. The overall survival and progression-free survival of patients with splenomegaly were significantly shorter than those of patients without splenomegaly (p < 0.01 and p = 0.02, respectively)., Conclusions: We concluded that splenomegaly was a predictor of prognosis in patients with PLC treated with ICIs. This is the first study to report this important finding., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

PURPOSE The high rate of recurrence of hepatocellular carcinoma (HCC) after radical hepatectomy is an important factor that affects the long-term survival of patients. This study aimed to develop a computed tomography (CT) images-based 3-dimensional (3D) convolutional neural network (CNN) for the preoperative prediction of early recurrence (ER) (≤2 years) after radical hepatectomy in patients with solitary HCC and to compare the effects of segmentation sampling (SS) and non-segmentation sampling (NSS) on the prediction performance of 3D-CNN. METHODS Contrast-enhanced CT images of 220 HCC patients were used in this study (training group=178 and test group=42). We used SS and NSS to select the volume-of-interest to train SS-3D-CNN and NSS-3D-CNN separately. The prediction accuracy was evaluated using the test group. Finally, gradient-weighted class activation mappings (Grad-CAMs) were plotted to analyze the difference of prediction logic between the SS-3D-CNN and NSS-3D-CNN. RESULTS The areas under the receiver operating characteristic curves (AUCs) of the SS-3D-CNN and NSS3D-CNN in the training group were 0.824 (95% CI: 0.764-0.885) and 0.868 (95% CI: 0.815-0.921). The AUC of the SS-3D-CNN and NSS-3D-CNN in the test group were 0.789 (95% CI: 0.637-0.941) and 0.560 (95% CI: 0.378-0.742). The SS-3D-CNN could stratify patients into low- and high-risk groups, with significant differences in recurrence-free survival (RFS) (P < .001). But NSS-3D-CNN could not effectively stratify them in the test group. According to the Grad-CAMs, compared with SS-3D-CNN, NSS-3D-CNN was obviously interfered by the nearby tissues. CONCLUSION SS-3D-CNN may be of clinical use for identifying high-risk patients and formulating individualized treatment and follow-up strategies. SS is better than NSS in improving the performance of 3D-CNN in our study.

Background: Immune checkpoint inhibitors (ICIs) have been used to successfully treat primary liver cancer (PLC); however, identifying modifiable patient factors associated with therapeutic benefits is challenging. Obesity is known to be associated with increased survival after ICI treatment; however, the relationship between body composition (muscle, fat) and outcomes is unclear. This study aimed to evaluate the association between sarcopenia and CT-derived fat content and the prognosis of ICIs for the treatment of PLC., Methods: In this retrospective cohort study of 172 patients with PLC, we measured the skeletal muscle index (SMI), skeletal muscle density, visceral adipose tissue index, subcutaneous adipose tissue index, total adipose tissue index (TATI), and visceral-to-subcutaneous adipose tissue area ratio using CT. In addition, we analyzed the impact of body composition on the prognosis of the patients. Multivariate Cox regression analysis was used to screen for influencing factors., Results: Among the seven body composition components, low SMI (sarcopenia) and low TATI were significantly associated with poor clinical outcomes. Multivariate analysis revealed that sarcopenia (hazard ratio [HR], 5.39; 95% confidence interval [CI], 1.74-16.74; p = 0.004) was a significant predictor of overall survival (OS). Kaplan-Meier curves showed that sarcopenia and TATI were significant predictors of OS. Body mass index was not associated with survival outcomes., Conclusions: Sarcopenia and fat tissue content appear to be independently associated with reduced survival rates in patients with PLC treated with ICIs., (© 2022. The Author(s).)

Background: Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC)., Methods: A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice., Results: Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045)., Conclusions: Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC., (© 2022. The Author(s).)

Background: Dyslipidemia is a significant contributor to cardiovascular and cerebrovascular diseases. Research on the relationship between breakfast consumption frequency and dyslipidemia in the working population is lacking. Therefore, we aimed to investigate this relationship based on a retrospective cohort study of a large working population in China., Methods: This retrospective cohort study used data from the physical examinations and questionnaire survey of working participants at Nanfang Hospital from January 20, 2015 to October 16, 2020. Univariate and multivariate analyses were conducted to explore the relationship between breakfast consumption frequency and dyslipidemia in this working population (n = 7644)., Results: The prevalence of dyslipidemia among the participants was 26.4%. The univariate logistic regression test showed that the breakfast consumption frequency was inversely correlated with dyslipidemia. After adjusting for multiple factors, such as sex, age, body mass index, hypertension, hyperuricaemia, diabetes, smoking status, alcohol consumption, education level, marital status, long-term exposure to kitchen oil fumes, attending business dinners, and sleep time, it was found that breakfast consumption remained inversely associated with dyslipidaemia. The odds ratio for daily breakfast consumption was 0.466 (95% confidence interval 0.283-0.770, P = 0.003). After adjusting for confounding factors, we found that the higher the frequency of breakfast consumption, the lower the odds ratios for hypertriglyceridaemia., Conclusions: This study demonstrated that breakfast consumption frequency was inversely correlated with dyslipidemia. The higher the frequency of breakfast, the lower the risk of hypertriglyceridaemia. This study provides a basis on which dietary suggestions for the working population and lifestyle guidance for patients with a clinical need to prevent dyslipidemia can be made., (© 2022. The Author(s).)

Background: At present, some cancer patients experience hyperprogressive disease (HPD) after receiving immunotherapy. This study used the Response Evaluation Criteria in Solid Tumors 1.1 to evaluate the incidence of HPD in patients receiving immune checkpoint inhibitors (ICIs) for treating primary liver cancer (PLC) and to explore the risk factors for HPD., Methods: This retrospective, single-center study included patients with PLC who were treated with ICIs. The RECIST 1.1 was used to determine patients with HPD. Univariate and multivariate regression analyses were performed to explore the risk factors for HPD, and clinical variables with prognostic significance for HPD were included to establish a risk model., Results: Among 129 patients with PLC treated with ICIs, HPD occurred in 13 patients (10.1%). In the multivariate regression analysis, lymph node metastasis and lung metastasis were risk factors for HPD. The area under the curve of the risk model, established by including lymph node metastasis, lung metastasis, neutrophil-lymphocyte ratio, albumin, and performance status, was 0.801 (P<0.001). The progression-free survival of HPD patients was significantly worse than that of non-HPD patients (P<0.001)., Conclusions: In this study, 10.1% of patients with PLC had HPD. Compared with the non-HPD patients, lung metastasis and lymph node metastasis were independent risk factors of HPD.

Objective: To clarify the correlation between temperature and the COVID-19 pandemic in Hubei. Methods: We collected daily newly confirmed COVID-19 cases and daily temperature for six cities in Hubei Province, assessed their correlations, and established regression models. Results: For temperatures ranging from -3.9 to 16.5°C, daily newly confirmed cases were positively correlated with the maximum temperature ~0-4 days prior or the minimum temperature ~11-14 days prior to the diagnosis in almost all selected cities. An increase in the maximum temperature 4 days prior by 1°C was associated with an increase in the daily newly confirmed cases (~129) in Wuhan. The influence of temperature on the daily newly confirmed cases in Wuhan was much more significant than in other cities. Conclusion: Government departments in areas where temperatures range between -3.9 and 16.5°C and rise gradually must take more active measures to address the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hu, Xiao, Zhu, Zhu and Liu.)

Background: Coronavirus disease (COVID-19) has swept around the globe and led to a worldwide catastrophe. Studies examining the disease progression of patients with non-severe disease on admission are scarce but of profound importance in the early identification of patients at a high risk of deterioration. Objectives: To elucidate the differences in clinical characteristics between patients with progressive and non-progressive COVID-19 and to determine the risk factors for disease progression. Study design: Clinical data of 365 patients with non-severe COVID-19 from 1 January 2020 to 18 March 2020 were retrospectively collected. Patients were stratified into progressive and non-progressive disease groups. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for disease progression. Results: Compared with patients with non-progressive disease, those who progressed to severe COVID-19 were older and had significantly decreased lymphocyte and eosinophil counts; increased neutrophil and platelet counts; lower albumin levels; higher levels of lactate dehydrogenase, C-reactive protein (CRP), creatinine, creatinine kinase, and urea nitrogen; and longer prothrombin times. Hypertension, fever, fatigue, anorexia, bacterial coinfection, bilateral patchy shadowing, antibiotic and corticosteroid administration, and oxygen support had a significantly higher incidence among patients with progressive disease. A significantly longer duration of hospital stay was also observed in patients with progressive disease. Bilateral patchy shadowing (OR = 4.82, 95% CI: 1.33-17.50; P = 0.017) and elevated levels of creatinine (OR =6.24, 95% CI: 1.42-27.40; P = 0.015), and CRP (OR = 7.28, 95% CI: 2.56-20.74; P < 0.001) were independent predictors for disease progression. Conclusion: The clinical characteristics of patients with progressive and non-progressive COVID-19 were significantly different. Bilateral patchy shadowing and increased levels of creatinine, and CRP were independent predictors of disease progression., (Copyright © 2020 Zhang, Xiao, Li, Zhu, Hu, Zhang, Sun, Shen, Liu, Zhang, Zeng, Gong, Liu, He and Zhu.)

Purpose: The aim of this study was to develop and validate a radiomics nomogram based on radiomics features and clinical data for the non-invasive preoperative prediction of early recurrence (≤2 years) in patients with hepatocellular carcinoma (HCC)., Methods: We enrolled 262 HCC patients who underwent preoperative contrast-enhanced computed tomography and curative resection (training cohort, n=214; validation cohort, n=48). We applied propensity score matching (PSM) to eliminate redundancy between clinical characteristics and image features, and the least absolute shrinkage and selection operator (LASSO) was used to prevent overfitting. Next, a radiomics signature, clinical nomogram, and combined clinical-radiomics nomogram were built to predict early recurrence, and we compared the performance and generalization of these models., Results: The radiomics signature stratified patients into low-risk and high-risk, which show significantly difference in recurrence free survival and overall survival (P ≤ 0.01). Multivariable analysis identified dichotomised radiomics signature, alpha fetoprotein, and tumour number and size as key early recurrence indicators, which were incorporated into clinical and radiomics nomograms. The radiomics nomogram showed the highest area under the receiver operating characteristic curve (AUC), with significantly superior predictive performance over the clinical nomogram in the training cohort (0.800 vs 0.716, respectively; P = 0.001) and the validation cohort (0.785 vs 0.654, respectively; P = 0.039)., Conclusion: The radiomics nomogram is a non-invasive preoperative biomarker for predicting early recurrence in patients with HCC. This model may be of clinical utility for guiding surveillance follow-ups and identifying optimal interventional strategies.

Objectives: Coronavirus disease 2019 (COVID-19) is sweeping the globe and has resulted in infections in millions of people. Patients with COVID-19 face a high fatality risk once symptoms worsen; therefore, early identification of severely ill patients can enable early intervention, prevent disease progression, and help reduce mortality. This study aims to develop an artificial intelligence-assisted tool using computed tomography (CT) imaging to predict disease severity and further estimate the risk of developing severe disease in patients suffering from COVID-19., Materials and Methods: Initial CT images of 408 confirmed COVID-19 patients were retrospectively collected between January 1, 2020 and March 18, 2020 from hospitals in Honghu and Nanchang. The data of 303 patients in the People's Hospital of Honghu were assigned as the training data, and those of 105 patients in The First Affiliated Hospital of Nanchang University were assigned as the test dataset. A deep learning based-model using multiple instance learning and residual convolutional neural network (ResNet34) was developed and validated. The discrimination ability and prediction accuracy of the model were evaluated using the receiver operating characteristic curve and confusion matrix, respectively., Results: The deep learning-based model had an area under the curve (AUC) of 0.987 (95% confidence interval [CI]: 0.968-1.00) and an accuracy of 97.4% in the training set, whereas it had an AUC of 0.892 (0.828-0.955) and an accuracy of 81.9% in the test set. In the subgroup analysis of patients who had non-severe COVID-19 on admission, the model achieved AUCs of 0.955 (0.884-1.00) and 0.923 (0.864-0.983) and accuracies of 97.0 and 81.6% in the Honghu and Nanchang subgroups, respectively., Conclusion: Our deep learning-based model can accurately predict disease severity as well as disease progression in COVID-19 patients using CT imaging, offering promise for guiding clinical treatment., (Copyright © 2020 Xiao, Li, Sun, Zhang, Xu, Zhu, Cai, He, Zhang, Ma, Hu, Gong, Liu, Shi and Zhu.)

Background: Information regarding risk factors associated with severe coronavirus disease (COVID-19) is limited. This study aimed to develop a model for predicting COVID-19 severity., Methods: Overall, 690 patients with confirmed COVID-19 were recruited between 1 January and 18 March 2020 from hospitals in Honghu and Nanchang; finally, 442 patients were assessed. Data were categorised into the training and test sets to develop and validate the model, respectively., Findings: A predictive HNC-LL (Hypertension, Neutrophil count, C-reactive protein, Lymphocyte count, Lactate dehydrogenase) score was established using multivariate logistic regression analysis. The HNC-LL score accurately predicted disease severity in the Honghu training cohort (area under the curve [AUC]=0.861, 95% confidence interval [CI]: 0.800-0.922; P<0.001); Honghu internal validation cohort (AUC=0.871, 95% CI: 0.769-0.972; P<0.001); and Nanchang external validation cohort (AUC=0.826, 95% CI: 0.746-0.907; P<0.001) and outperformed other models, including CURB-65 (confusion, uraemia, respiratory rate, BP, age ≥65 years) score model, MuLBSTA (multilobular infiltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hypertension, and age) score model, and neutrophil-to-lymphocyte ratio model. The clinical significance of HNC-LL in accurately predicting the risk of future development of severe COVID-19 was confirmed., Interpretation: We developed an accurate tool for predicting disease severity among COVID-19 patients. This model can potentially be used to identify patients at risks of developing severe disease in the early stage and therefore guide treatment decisions., Funding: This work was supported by the National Nature Science Foundation of China (grant no. 81972897) and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015)., Competing Interests: Declaration of Competing Interest The authors declare that they do not have any conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Urban sprawl has impacted increasingly on water environment quality in watersheds. Based on water environmental response, the simulation and prediction of expanding threshold of urban building land could provide an alternative reference for urban construction planning. Taking three watersheds (i.e., Yundang Lake at complete urbanization phase, Maluan Bay at peri-urbanization phase and Xinglin Bay at early urbanization phase) with 2009-2012 observation data as example, we calculated the upper limit of TN and TP capacity in three watersheds and identified the threshold value of urban building land in watersheds using the regional nutrient management (ReNuMa) model, and also predicted the water environmental effects associated with the changes of urban landscape pattern. Results indicated that the upper limit value of TN was 12900, 42800 and 43120 kg, while that of TP was 340, 420 and 450 kg for Yundang, Maluan and Xinglin watershed, respectively. In reality, the environment capacity of pollutants in Yundang Lake was not yet satura-ted, and annual pollutant loads in Maluan Bay and Xinglin Bay were close to the upper limit. How-ever, an obvious upward trend of annual TN and TP loads was observed in Xinglin Bay. The annual pollutant load was not beyond the annual upper limit in three watersheds under Scenario 1, while performed oppositely under Scenario 3. Under Scenario 2, the annual pollutant load in Yundang Lake was under-saturation, and the TN and TP in Maluan Bay were over their limits. The area thresholds of urban building land were 1320, 5600 and 4750 hm 2 in Yundang Lake, Maluan Bay and Xinglin Bay, respectively. This study could benefit the regulation on urban landscape planning.

Objective: To investigate the expression of microRNA-107 (miR-107) and its functional role in hepatocellular carcinoma(HCC)., Methods: The gene chip data of HCC obtained from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database were used to analyze the expression levels of miR-107 in liver cancer. Twenty-two pairs of fresh surgical specimens of HCC and adjacent tissues and 53 paraffin-embedded specimens of HCC were examined for miR-107 expression by qRT-PCR. The correlation of the expression levels of miR-107 with the clinicopathologic characteristics of the patients were analyzed. The role of miR-107 in regulating the proliferation of hepatocellular carcinoma cells were determined by MTT assay in Huh7 cells transfected with a miR-107 mimic or inhibitor., Results: The expression levels of miR-107 were significantly up-regulated in HCC tissues as compared to the adjacent tissues (P<0.05) in positive correlation with the tumor size (P<0.032). Transfection with miR-107 mimics significantly promoted the cell proliferation (P<0.0001) while miR-107 inhibitor inhibited the cell proliferation (P<0.0001)., Conclusion: The expression of miR-107 is up- regulated in HCC tissues and its expression levels are correlated with HCC cell proliferation, suggesting its role as a potential oncogene in liver cancer.

Objective: To investigate the RHD zygosity distribution and the genetic characteristics of RHD gene in the Dong ethnic population in southeast area of Guizhou province., Methods: Based on the characteristics of Chinese RHD and the RHD specific deletion, two pairs of primers specific for hybrid Rhesus box and exon 1 of RHD respectively, were designed, combined with a pair of internal control primers. Polymerase chain reaction was performed to genotype the samples., Results: In the 292 RhD positive samples, 58 (19.86%) were RHD+/RHD- heterozygotes, and the others (80.14%) were RHD+/RHD+ homozygotes. In the 9 D negative samples, 5 were RHD+/RHD- heterozygotes (2 weak D, 3 Del), 3 were RHD+/RHD+ homozygotes (1weak D, 2 Del), and 1 was RHD-/RHD- homozygote., Conclusion: RHD+/RHD- heterozygosity is higher (19.86%) in D positive individuals of Dong ethnic group in Guizhou province than that in other areas; RHD gene heterozygosity is also high in the D negative individuals in this ethnic group.

Acetylcholinesterace (AChE) is known to be the major target for organophophate and carbamate insecticides and biomolecular changes to AChE have been demonstrated to be an important mechanism for insecticide resistance in many insect species. In this study, AChE from three field populations of Liposcelis entomophila (Enderlein) (Psocoptera: Liposcelididae) was purified by affinity chromatography and subsequently characterized by its Michaelis-Menten kinetics to determine if detectable changes to AChE have occurred. Bioassays revealed that the potential resistance threat of psocids in Sichuan Province (GH) was greater than either Hubei Province (WH) or Chongqing Municipality (BB). Compared to the other two populations, the WH population possessed the highest specific activity of purified AChE. Kinetic analyses indicated that the purified AChE from GH population expressed a significantly lower affinity to the substrate and a higher catalytic activity toward acetylthiocholine iodide (ATChI) (i.e., higher K(m) and V(max) values) than BB and WH populations. In vitro studies of AChE suggest that five inhibitors (aldicarb, eserine, BW284C51, omethoate, and propoxur) all possess strong inhibitory effects with eserine having the strongest inhibitory effect against purified AChE. According to bimolecular rate constants (k(i)), the purified AChE from GH population was least sensitive to all inhibitors except for omethoate. The differences in AChE among the three populations may be partially attributed to the differences in pesticide application and control practices for psocids among the three locations., (© 2010 Wiley Periodicals, Inc.)

Endosymbiotic bacteria that potentially influence reproduction and other fitness-related traits of their hosts are widespread in arthropods, and their appeal to researchers' interest is still increasing. In this study, the effects of removal of Cardinium infection on development, survival, and reproduction of Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae) were investigated in the laboratory. The Cardinium-free strain was obtained by the removal of Cardinium infection by using 1% rifampicin treatment on the Cardinium-infected strain (control) for 4 wk, and no Cardinium gene product was detected in this strain throughout the experiment. The results showed that the removal of Cardinium infection had negative effects on fitness of L. bostrychophila. Compared with the control strain, the Cardinium-free strain (both in first [F1] and second [F2] generation) had a similar developmental time, reduced survivorship of immature stages, as well as reduced fecundity, which resulted in much smaller r(m) values. Using r(m) values, the fitness for Cardinium-free F1 and F2 relative to the control was calculated as 0.81 and 0.74, respectively. We concluded that the use of antibiotics combined with heat treatment might be a good control measure for L. bostrychophila.

Aim: To evaluate the effect of FcgammaRIIB(1) (CD32) representative self-inhibitory adjustive mechanism of B cells on pathogenesis of systemic lupus erythematosus (SLE) by observing the expression characteristic and functional state of molecules on the surface of B cells from SLE patients., Methods: The peripheral blood mononuclear cells (PBMC) were prepared by density gradient centrifugation, and the B cells were isolated from PBMC by magnetic activated cell sorting (MACS). The fluxes of intracytoplasmic calcium ([Ca(2+)](i)) of B cells activated by different activators were measured by fluorescence spectrophotometric method. The IgG production by B cells cultured with activators was assayed by ELISA. The expression levels of CD32, CD19, and IgM on the surface of B cells were measured by flow cytometry., Results: (1)After B cells were stimulated with goat anti-human mu chain F(ab')(2) fragments and whole IgG respectively, the ratio of [Ca(2+)](i) response by F(ab')(2) fragments to whole IgG was significantly lower in SLE B cells compared to rheumatoid arthritis (RA)(P<0.05) or normal (P<0.01) B cells. (2)The ratio of total IgG production by B cells cultured with staphylococcal protein A (SPA) to SPA plus IgG anti-mu chain was significantly lower in SLE patients compared to RA patients or normal individuals (P<0.05). (3)There was no obvious difference in the expression of CD19, CD32, and IgM on the surface of B cells from SLE, RA patients and normal individuals (P>0.05)., Conclusion: The inhibitory signaling abnormality of CD32 possibly contributes to the mechanism of hyperactivity of human SLE B cells.

The absolute configuration of the (+)-1,1-dimethyl-2-phenylethyl phenyl sulfoxide is determined to be (R), using three different chiroptical spectroscopic methods, namely vibrational circular dichroism (VCD), electronic circular dichroism (ECD) and specific rotation. Four solution conformations are identified for 1,1-dimethyl-2-phenylethyl phenyl sulfoxide. In each of the methods used, experimental data for the enantiomers of 1,1-dimethyl-2-phenylethyl phenyl sulfoxide were measured in the solution phase and concomitant quantum mechanical calculations of corresponding properties were carried out using density functional theory with B3LYP functional and 6-31G* and 6-31+G basis sets. Additional VCD and ECD calculations were also undertaken with 6-311G(2d,2p) basis set. A comparison of theoretically predicted data with the corresponding experimental data has allowed us to elucidate the absolute configuration and predominant conformations of (+)-1,1-dimethyl-2-phenylethyl phenyl sulfoxide.

Although interracial differences of prostate cancer progression are well recognized, their underlying molecular and cellular mechanisms remain obscure. We compared the histopathologic, immunohistochemical, and molecular characteristics of unselected prostate cancer tissues obtained from U.S., Chinese, and Japanese men. Histopathologic analyses indicated that 74.4% of the prostate cancers in Chinese men were poorly differentiated, compared with 28.6% and 32.8% of the prostate cancers in U.S. and Japanese men, respectively. These differences cannot be attributed to patient age, clinical stage of disease, or methods of tissue sampling. The high proportion of poorly differentiated prostate cancer tissues in the Chinese group was not related to the patients' access to medical service or to geographic background within China. Significantly higher levels of tumor angiogenesis (2- to 4-fold), serotonin (2- to 20-fold), and bombesin (7- to 16-fold), but not chromogranin A, were found in the tissue specimens obtained from Chinese prostate cancer patients compared with those from U.S. and Japanese patients. We also observed marked interracial differences in p53 protein accumulation. The protein was present in 90.2% of Chinese specimens; 17.4% of specimens from U.S. whites; 7.1% of specimens from Japanese men; and 3.7% of specimens from U.S. blacks. Results from multivariate logistic regression analysis demonstrated that p53 protein accumulation, angiogenesis, and serotonin expression in the normal stroma area correlate independently with Chinese versus non-Chinese patient populations.

Clinical and statistical investigations were performed on 157 patients with prostate carcinoma in the Third Teaching Hospital, Normal Bethune University experienced between January, 1950 and June, 1986. The number of patients with prostate carcinoma among other hospitalized patients showed a recent gradual increase. The patient's age at the time the disease was first diagnosed was most frequently between 60 and 69 years old with an average age of 63.3 years. Dysuria was the most prominent symptom, followed by frequency, retention and macroscopic hematuria. Duration between initial symptom and diagnosis was one to two years in most patients. The prostatic abnormality could be detected by rectal examination in all patients. Elevation of serum acid phosphatase was found in 24.4%. Such elevation was evident in 52.2% of the patients with metastatic lesions, compared to 14.4% of those without metastasis. Fourteen patients had metastasis to bone (8.9%), 13 to lymph nodes, 2 to lung and one to liver. According to the staging diagnosis, 19 patients (12.1%) had stage A, 78 patients (49.7%) had stage B, 20 patients (12.7%) had stage C and 40 patients (25.5%) had stage D carcinoma. Histological findings in 57 patients indicated adenocarcinomas; 39 cases (68.4%) were poorly differentiated, 12 cases (21.2%) were moderately differentiated and 6 cases (10.5%) were well differentiated. Modality of treatment was total prostatectomy in 2 cases (1.3%), antiandrogen therapy (orchiectomy and/or Stilbestrol) in 122 cases (77.7%), subcapsular prostatectomy in 7 cases (4.5%), symptomatic treatment in 5 cases and no treatment in 23 cases (14.6%).