Integrated analysis reveals important differences in the gut and oropharyngeal microbiota between children with mild and severe hand, foot, and mouth disease.

Little is known about alternation and difference in gut microbiota between patients with mild and severe hand, foot, and mouth disease (HFMD). We investigated the differences in gut and oropharynx microbiota between mild and severe HFMD in young children and changes in bacterial profiles as the disease progresses from acute to convalescent phase. Forty-two patients with confirmed HFMD were studied, among which 32 had severe HFMD and 10 had mild HFMD. First rectal swabs were collected from all patients at an average of 2 days (acute phase) after the onset of symptoms, and second rectal swabs were collected from 8 severe patients at day 9 (convalescent phase) after the onset. Oropharyngeal swabs were obtained from 10 patients in the acute phase and 6 in the convalescent phase. 16S rRNA sequencing was performed for all 70 samples. Compared with mild HFMD, severe HFMD exhibited significantly decreased diversity and richness of gut microbiota. Gut microbiota bacterial profiles observed in the acute and convalescent phases resembled each other but differed from those in mild cases. Additionally, 50% of patients with severe HFMD in the acute phase harboured a dominant pathobiontic bacterial genus. However, none of the patients with mild HFMD had such bacteria. Similar bacterial compositions in oropharynx microbiota were detected between mild and severe cases. Our findings indicate that severe HFMD exhibits significantly impaired diversity of gut microbiota and frequent gut and oropharyngeal inflammation-inducing bacteria. However, the results should be interpreted with caution as the number of subjects was limited.

Clinical features and survival analysis of 97 coronavirus disease 2019 (COVID-19) patients.

BACKGROUND: We aim to investigate the clinical characteristics and survival rate of coronavirus disease 2019 (COVID-19) patients. METHODS: Ninety-seven COVID-19 patients were enrolled. The laboratory results, lung imaging and medical treatment were compared. Patients were followed up after 1 year, and the Kaplan-Meier test was used for survival analysis. RESULTS: Compared with the non-severe group, the age of the severe group was older, and the proportion of concomitant diseases were higher. As fever was the primary clinical manifestation, dyspnea and anorexia were more common in severe patients. Lung imaging manifestations and laboratory indicators were worse in the severe group. Accordingly, the treatment of glucocorticoid, antibiotics, and advanced life support were in high proportion. Of the 97 patients with COVID-19, 4 severe patients died within one month during the 1-year follow-up, with the median survival time of 47.0 weeks (95% CI: 45.1-48.9). CONCLUSIONS: Severe cases of COVID-19 are characterized by advanced age, more concomitant diseases and complications, which lead to a decreased short-term survival rate. However, there were no deaths after one month, which implied a good prognosis if the risk period were passed smoothly.

Texture feature-based machine learning classifier could assist in the diagnosis of COVID-19.

PURPOSE: Differentiating COVID-19 from other acute infectious pneumonias rapidly is challenging at present. This study aims to improve the diagnosis of COVID-19 using computed tomography (CT). METHOD: COVID-19 was confirmed mainly by virus nucleic acid testing and epidemiological history according to WHO interim guidance, while other infectious pneumonias were diagnosed by antigen testing. The texture features were extracted from CT images by two radiologists with 5 years of work experience using modified wavelet transform and matrix computation analyses. The random forest (RF) classifier was applied to identify COVID-19 patients and images. RESULTS: We retrospectively analysed the data of 95 individuals (291 images) with COVID-19 and 96 individuals (279 images) with other acute infectious pneumonias, including 50 individuals (160 images) with influenza A/B. In total, 6 texture features showed a positive association with COVID-19, while 4 features were negatively associated. The mean AUROC, accuracy, sensitivity, and specificity values of the 5-fold test sets were 0.800, 0.722, 0.770, and 0.680 for image classification and 0.858, 0.826, 0.809, and 0.842 for individual classification, respectively. The feature 'Correlation' contributed most both at the image level and individual level, even compared with the clinical factors. In addition, the texture features could discriminate COVID-19 from influenza A/B, with an AUROC of 0.883 for images and 0.957 for individuals. CONCLUSIONS: The developed texture feature-based RF classifier could assist in the diagnosis of COVID-19, which could be a rapid screening tool in the era of pandemic.

Clinical characteristics and outcomes in elderly with coronavirus disease 2019 in Beijing, China: a retrospective cohort study.

A novel human coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic of coronavirus disease 2019 (COVID-19). In this study, we aimed to explore the clinical characteristics and outcomes in older patients with COVID-19. Ninety-one patients with SARS-CoV-2 infection were included in the study, 27 of which (29.67%) were elderly. The median age of these 27 patients was 74.9 years (interquartile range 68-82; range 65-94 years), and 15 (55.56%) were female. Elderly with COVID-19 in Beijing (China) were more likely to have underlying comorbidities and more frequently tended to have critical illness and suffer from more complications. The main treatments of the elderly consisted of symptomatic and respiratory support. The most frequent complications in the elderly were pleural effusion [10, (37.04%)], secondary infection [7, (25.93%)], and kidney damage [7, (25.93%)]. Six (22.22%) of the 27 elderly patients received invasive ventilation (three of them switched to extracorporeal membrane oxygenation). As of March 7, 20 (74.07%) of the 27 elderly patients were discharged, two (7.41%) were still hospitalized, and five died; the mortality in the elderly was 18.52%. Age was associated with the mortality in patients with COVID-19 (OR 0.82; 95% CI 0.70-0.97; P = 0.019). Therefore, more attention should be paid to the treatment of comorbidities and complications in elderly patients.

Duration of SARS-CoV-2 RNA shedding and factors associated with prolonged viral shedding in patients with COVID-19.

To investigate the factors associated with the duration of severe acute respiratory syndrome coronavirus 2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). A retrospective cohort of COVID-19 patients admitted to a designated hospital in Beijing was analyzed to study the factors affecting the duration of viral shedding. The median duration of viral shedding was 11 days (IQR, 8-14.3 days) as measured from illness onset. Univariate regression analysis showed that disease severity, corticosteroid therapy, fever (temperature>38.5°C), and time from onset to hospitalization were associated with prolonged duration of viral shedding (P < .05). Multivariate regression analysis showed that fever (temperature>38.5°C) (OR, 5.1, 95%CI: 1.5-18.1), corticosteroid therapy (OR, 6.3, 95%CI: 1.5-27.8), and time from onset to hospitalization (OR, 1.8, 95%CI: 1.19-2.7) were associated with increased odds of prolonged duration of viral shedding. Corticosteroid treatment, fever (temperature>38.5°C), and longer time from onset to hospitalization were associated with prolonged viral shedding in COVID-19 patients.

Preliminary Exploration of the Cause of Liver Disorders During Early Stages in COVID-19 Patients.

Background: Abnormal liver function is a common indication of coronavirus disease 2019 (COVID-19) patients. Two proposed mechanisms are liver injury mediated by angiotensin-converting enzyme 2 (ACE2) and the involvement of the systemic immune response. We investigated the role played by these to determine the cause of liver abnormality in the early stages of COVID-19. Methods: A cross-sectional study was conducted among confirmed cases of COVID-19 at Beijing Youan Hospital from January 21, 2020, to February 24, 2020. We compared clinical characteristics, viremia status, and cytokine profile on admission between patients with and without liver disorder. Results: Of the 44 COVID-19 patients analyzed, there were no differences in the clinical symptoms and signs, disease severity, or computed tomography (CT) image features between the two groups. Lymphopenia was more common in the liver disorder group. Further, C-reactive protein levels were much higher in the hepatic disorder group, with significantly higher concentrations of IL-6, IL-10, and M-CSF. Viremia was detected in only 7% of patients. Conclusions: Due to the infrequency of viremia, ACE2-mediated viral hepatitis does not seem to account for the commonly observed liver disorders in COVID-19 patients. By contrast, a dysregulated immune response may be a crucial pathogenic factor for liver disorder in the early stages of COVID-19.

Clinical characteristics of patients diagnosed with COVID-19 in Beijing.

This study aimed to determine the clinical characteristics of patients diagnosed with the coronavirus disease 2019 (COVID-19). Clinical data of COVID-19 patients diagnosed between January 28, 2020 and February 23, 2020 at the Beijing You'an Hospital were summarized and analyzed. Overall, 45 (18 men and 27 women) patients were included in this study. The average age of patients was 58 years (range, 7-94 years). Furthermore, 21 patients (47%) experienced underlying chronic diseases, with another four patients (9%) having three or more chronic diseases simultaneously. The first symptoms appeared at the onset of illness onset include fever in 36 patients (80%), cough in 23 patients (51%), and expectoration in 15 patients (33%), respectively. Patients may experience hepatic and renal injury as well as abnormal myocardial enzymes in varying degrees. Senior patients (≥58) and accompanying chronic diseases were considered as independent predictors for developing a severe and critically ill population with increased mortality. Laboratory results regarding the NEU percentage, NLR, ALC, and C-reactive protein levels were considered significant in predicting clinically critical disease or for prognosis assessment and thus require further studies. COVID-19 may affect multiple organs of the human body. Glucocorticoid is considered effective in the treatment of patients diagnosed with severe COVID-19.

Clinical characteristics of Coronavirus Disease 2019 patients in Beijing, China.

The outbreak of Coronavirus Disease (COVID-19) in Wuhan have affected more than 250 countries and regions worldwide. However, most of the clinical studies have been focused on Wuhan, and little is known about the disease outside of Wuhan in China. In this retrospective cohort study, we report the early clinical features of 80 patients with COVID-19 admitted to the hospital in Beijing. The results show that 27 (33.8%) patients had severe illness. Six (7.5%) patients were admitted to the ICU, and 3 (3.8%) patients died. Forty-eight percent (39/80) of the patients had a history of living/traveling in Wuhan. Patients with severe- illness were significantly older (average age, 71 years old vs 44 years old) and had a high incidence of expectoration (59.3% vs 34.0%), shortness of breath (92.6% vs 9.4%), anorexia (51.9% vs 18.9%) and confusion(18.5% vs 0%) compared with nonsevere patients. The systolic blood pressure (median, 130 mmHg vs 120 mmHg) was higher and the oxygen saturation (median, 98.3% vs 92.0%) was significantly lower in severe patients than nonsevere patients. In addition, myoglobin (median, 56.0 ng/mL vs 35.0 ng/mL), troponin I (median, 0.02 pg/mL vs 0.01 pg/mL), C-reactive protein (median, 69.7 mg/L vs 12.9 mg/L) and neutrophils (median, 3.3×109/L vs 2.2×109/L) were significantly increased, while lymphocytes (median, 0.8×109/L vs 1.2×109/L), albumin (mean, 32.8 g/L vs 36.8 g/L) and the creatinine clearance rate (median, 91.2 vs 108.2 ml/min/1.73m2) were significantly decreased among severe patients. Our study revealed that older patients with high levels of C-reactive protein, myoglobin, troponin I, and neutrophil and high systolic blood pressure as well as low levels of lymphocytes, and albumin and a low creatinine clearance rate and oxygen saturation were more likely to have severe disease.

Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease.

BACKGROUND: Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation, and drug development. Here, we present a temporal analysis of key immune mediators, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 weeks. METHODS: A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You'an Hospital in China with either mild (53 patients) or severe (18 patients) disease were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines, and chemokines in peripheral blood every 4-7 days over 1 month per patient using a bioplex multiplex immunoassay. RESULTS: We found that the chemokine RANTES (CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity, and a combination of CCL5, IL-1 receptor antagonist (IL-1RA), and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-γ were only significantly elevated in the late stage of severe COVID-19 illness. TNF-α and GM-CSF showed no significant differences between severe and mild cases. CONCLUSION: Together, our data suggest that early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1RA and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.

A Novel Scoring System for Prediction of Disease Severity in COVID-19.

Background: A novel enveloped RNA beta coronavirus, Corona Virus Disease 2019 (COVID-19) caused severe and even fetal pneumonia in China and other countries from December 2019. Early detection of severe patients with COVID-19 is of great significance to shorten the disease course and reduce mortality. Methods: We assembled a retrospective cohort of 80 patients (including 56 mild and 24 severe) with COVID-19 infection treated at Beijing You'an Hospital. We used univariable and multivariable logistic regression analyses to select the risk factors of severe and even fetal pneumonia and build scoring system for prediction, which was validated later on in a group of 22 COVID-19 patients. Results: Age, white blood cell count, neutrophil, glomerular filtration rate, and myoglobin were selected by multivariate analysis as candidates of scoring system for prediction of disease severity in COVID-19. The scoring system was applied to calculate the predictive value and found that the percentage of ICU admission (20%, 6/30) and ventilation (16.7%, 5/30) in patients with high risk was much higher than those (2%, 1/50; 2%, 1/50) in patients with low risk (p = 0.009; p = 0.026). The AUC of scoring system was 0.906, sensitivity of prediction is 70.8%, and the specificity is 89.3%. According to scoring system, the probability of patients in high risk group developing severe disease was 20.24 times than that in low risk group. Conclusions: The possibility of severity in COVID-19 infection predicted by scoring system could help patients to receiving different therapy strategies at a very early stage. Topic: COVID-19, severe and fetal pneumonia, logistic regression, scoring system, prediction.

Risk factors for disease progression in hospitalized patients with COVID-19: a retrospective cohort study.

Background: To investigate the risk factors related to aggravation and clinical outcomes in coronavirus disease 2019 (COVID-19) patients.Methods: We performed a retrospective study on the risk factors for disease progression of cases with COVID-19. Based on the clinical types, the patients were divided into a progression group and an improvement group. Multivariable logistic regression and ROC curve analysis were performed to explore the risk factors for disease progression.Results: A total of 101 patients were included in this study; diseases progression occurred in 17 patients, 84 patients improved, 6 were transferred to intensive care unit (ICU), and 5 died. The mean time to obtain negative nucleic acid results was 12.5 ± 5.0 days. Multivariate logistic analysis indicated that age (OR, 0.104; p = .002), C-reactive protein (CRP) (OR, 0.093; p < .001) and lymphocyte count (OR, 3.397; p = .022) were risk factors for disease progression. ROC curve analysis revealed that the AUC of age, CRP and lymphocyte count for disease progression were 0.873, 0.911 and 0.817, respectively.Conclusions: Older age increased CRP and decreased lymphocyte count resulted in potential risk factors for COVID-19 progression. This may be helpful in identifying patients whose condition worsens at an early stage.

Interferon-Induced Transmembrane Protein 3 Genetic Variant rs12252-C Associated With Disease Severity in Coronavirus Disease 2019.

A major unanswered question in the current global coronavirus disease 2019 (COVID-19) outbreak is why severe disease develops in a small minority of infected individuals. In the current article, we report that homozygosity for the C allele of rs12252 in the interferon-induced transmembrane protein 3 (IFITM3) gene is associated with more severe disease in an age-dependent manner. This supports a role for IFITM3 in disease pathogenesis and the opportunity for early targeted intervention in at-risk individuals.

Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of Neutrophil Activation.

Andrographolide sulfonate treatment has been shown to improve clinical severe hand, foot, and mouth disease (HFMD) efficacies when combined with conventional therapy. However, the mechanisms for its therapeutic effects remain elusive. In this study, we aimed to investigate whether andrographolide sulfonate exerts its efficacy by acting on neutrophil activation. We obtained serial plasma samples at two time points (before and after 5 days of therapy) from 28 HFMD patients who received conventional therapy and 18 patients who received combination therapy (andrographolide sulfonate plus conventional therapy). Then, we measured plasma myeloperoxidase (MPO), S100A8/A9, histone, and inflammatory cytokine levels. Furthermore, we examined if andrographolide sulfonate had direct effects on neutrophil activation in vitro. We observed that MPO and S100A8/A9 levels were markedly elevated in the HFMD patients before clinical treatment. At 5 days post-medication, the MPO, S100A8/A9, histone, and interleukin-6 levels were markedly lower in the combination therapy group compared with the conventional therapy group. In vitro studies showed that andrographolide sulfonate inhibited lipopolysaccharide-stimulated neutrophil activation, demonstrated by the decreased production of reactive oxygen species and cytokines. These data indicate that neutrophil activation modulation by andrographolide sulfonate may be a critical determinant for its clinical HFMD treatment efficacy. Copyright © 2015 John Wiley & Sons, Ltd.

A new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease.

This study aimed to find novel information concerning pathogen detection and some probable coinfection factors in hand, foot, and mouth disease (HFMD). In this study, 1104 clinically diagnosed HFMD patients were included. Enterovirus 71 (EV71), coxsackievirus A16 (CA16), and 14 different respiratory pathogens were examined from nasopharyngeal swabs using polymerase chain reaction (PCR) or reverse transcriptase PCR (RT-PCR). To evaluate the immune activation in HFMD patients, 8 cytokines and IgM antibodies to EV71 and CA16 from mild and severe patients were detected. Our results indicated that the severity of HFMD may affect the pathogen detection. The lower positive rates of enterovirus and respiratory viruses in severe HFMD cases by RT-PCR were probably related to stronger immune response. Therefore, immunological tests such as ELISA are essential supplements to PCR or RT-PCR in order to increase pathogen diagnosis in HFMD, especially in severe cases.

Natural herbal medicine Lianhuaqingwen capsule anti-influenza A (H1N1) trial: a randomized, double blind, positive controlled clinical trial.

BACKGROUND: The 2009 influenza A (H1N1) virus infection is associated with the high risk of severe complications and is spreading more rapidly throughout the world than other reported seasonal influenzas. This study aimed to evaluate the efficacy and safety of the nature herbal medicine Lianhuaqingwen capsule (LHC) in patients infected with influenza A (H1N1) virus. METHODS: A total of 244 patients aged 16 - 65 years confirmed with influenza A (H1N1) virus infection by the real time RT-PCR were randomized to one of two treatment groups of 122 patients each. Each group assigned to receive either LHC or Oseltamivir for five days and observation for seven days. The patients were enrolled within 36 hours of illness onset if they had an axillary temperature of ≥ 37.4°C and with at least one of the following symptoms: nasal obstruction, runny nose, cough, sore throat, fatigue, headache, myalgia, chills and sweating. The primary end point was the duration of illness. RESULTS: Of 244 patients, 240 (98.36%) patients with a median age 21 years completed the study between October 24, 2009 and November 23, 2009. There were no significant overall differences between LHC treated and Oseltamivir treated patients in the median duration of illness (LHC 69 hours vs. Oseltamivir 85 hours P > 0.05) or the median duration of viral shedding (LHC 103 hours vs. Oseltamivir 96 hours, P > 0.05). However, it was worthwhile to note that LHC significantly reduced the severity of illness and the duration of symptoms including fever, cough, sore throat, and fatigue (P < 0.05). Both study medications were well tolerated. No drug related serious adverse events occurred during the study. CONCLUSIONS: Compared with Oseltamivir, LHC achieved a similar therapeutic effectiveness reduction of the duration of illness and duration of viral shedding. Therefore, LHC might be an alternative therapeutic measure for influenza A (H1N1) virus infections.

Epidemiological and clinical features of 308 hospitalized patients with novel 2009 influenza A (H1N1) virus infection in China during the first pandemic wave.

OBJECTIVES: To investigate the epidemiological and clinical features of 308 hospitalized patients suffering from infection with novel H1N1 influenza virus in China from May to August 2009, and to examine the effects of oseltamivir treatment for mild cases. METHODS: Information on H1N1 influenza patients confirmed by real-time RT-PCR assay was gathered and analyzed from an influenza surveillance system, including demographic features, clinical symptoms and signs, therapeutic regimen, and duration of fever and virus shedding. RESULTS: The clinical course of infected individuals appeared mild. Mainly young adults were affected. Most cases had low or mid-level fever, cough, headache, rhinorrhoea, and sore throat. Few patients had vomiting (1.3%) and diarrhea (3.9%). Oseltamivir treatment did not shorten the duration of fever. Furthermore, early oseltamivir treatment as well as early conventional supportive treatment without antiviral drugs contributed to a reduction in the duration of virus shedding. CONCLUSIONS: In the first pandemic wave, novel H1N1 virus caused disease primarily in adults, causing mild febrile illness. Mildly ill patients cleared the virus rapidly even in the absence of oseltamivir treatment.

[The analysis of clinical character in different age patients suffered from A-H1N1].

OBJECTIVE: To describe the feature of different age patients with A-H1N1. METHODS: Cross-sectional study was performed in 95 patients who were confirmed to be infected with A-H1N1 from May, 2009 to July, 2009, in according to their age. RESULTS: The average age of patients with A-H1N1 infection was 23.44 +/- 14.73. Accumulative prevalence in children and young adult reached 74.7% of total patients. There was a trend that the subclinical infection rate raised gradually from 0-15 years group to over 45 years group. The percent of lymphocyte in 0-15 years group was significantly higher than other age groups, P = 0.039. The average time of virus shedding were 6.5 +/- 2.10 days (from 2 days to 12 days) , and there were no significant difference in diverse age groups, P = 0.272. 13 out of 95 (13.7%) patients presented complications related with A-H1N1 infection, and 4 of 6 patients complicated with pneumonia were in the 0-15 years group. CONCLUSION: The distribution of age in A-H1N1 infection is markedly different from seasonal influenza, with more cases in school children and young adults and fewer cases in older adults. Flu-like symptoms in children were apparent and pneumonia was the major complication in children.

[A clinical analysis of 137 cases of influenza A(H1N1)].

OBJECTIVE: To analyze the epidemiology and clinical characteristics of influenza A (H1N1). METHODS: A retrospective analysis was performed on the clinical data of 137 cases of influenza A (H1N1) admitted into our hospital during May to August 2009. RESULTS: In the early stage, most cases were imported from the US, Australia, Canada and the UK. While in the later stage, most of them were secondary. The patients were mainly children and youngsters. And the most common clinical manifestations were fever (n = 108), cough (n = 93) and sore throat (n = 67) while the most common signs congestive throat (n = 99) and swelling tonsil (n = 46). The average fever period was 3.3 ± 1.5 days. The clinical symptoms vanished in 4.4 ± 1.9 days. And the average length of stay was 5.5 ± 2.1 days. Laboratory tests: the count of leukocytes declined while that of lymphocytes increased in 39 cases (39.5%). The test of influenza A (H1N1) nucleic acid was positive. The chest radiograph showed intensive pulmonary markings or patchy pneumonia-like signs. TREATMENTS: the groups of patients using Chinese herbs, western medicine plus Chinese herbs, symptomatic relief and placebo showed no significant difference in fever period, recovery time and the negative-converting period of influenza A (H1N1) nucleic acid tests became negative. CONCLUSION: Influenza A (H1N1) may be recessive or dominant. Despite a strong infectivity, the clinical symptoms are mild and the clinical course is self-limited, similar to the seasonal influenza.

[E2F1 upregulates endogenous XRCC1 expression].

OBJECTIVE: To investigate the regulatory effect and significance of transcription factor E2F1 on X-ray repair cross2 complementing 1 (XRCC1). METHODS: Saos2 cells were transfected with the E2F1 expression vectors (tet-E2F1) and mutated E2F1 expression vectors (tet-132E). XRCC1 promotor luciferase reporter vector was constructed and transfected into Saos2 cells together with E2F1, E2F2, E2F3 and E2F4 expression vectors at different amount. The cells were collected 36 hours post-transfection for luciferase assays and absorbance was read at 570 nm. RESULTS: Cotransfection of increasing amounts of E2F1 expression vector with the XRCC1 promoter-luciferase reporter caused a dose-dependent increase in luciferase activation. In contrast, DNA binding incompetent E2F1 (132E) could not activate the XRCC1 promoter-luciferase reporter. CONCLUSION: E2F1 could upregulate endogenous XRCC1 expression and stimulate the XRCC1 promoter.