Distinguishing features of long COVID identified through immune profiling.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

Safety and Effectiveness of Rasburicase in the Control of Hyperuricemia in Pediatric Patients with Non-Hodgkin's Lymphoma and Acute Leukemia: An Open-Label, Single-Arm, Multi-center, Interventional Study.

INTRODUCTION: Despite rasburicase's proven efficiency in Caucasians, Japanese, and Koreans, studies evaluating the safety and effectiveness of rasburicase in Chinese pediatric patients with non-Hodgkin's lymphoma (NHL) and acute leukemia (AL) in particular are lacking. OBJECTIVE: The aim was to evaluate the safety and effectiveness of rasburicase in Chinese pediatric patients with NHL and AL. METHODS: In this phase IV, open-label, non-randomized, single-arm, multi-center, interventional study (NCT04349306), children newly diagnosed with NHL or AL who received 0.20 mg/kg/day of rasburicase were included. The primary objective was to assess the safety of rasburicase by the incidence of adverse events (AEs). The secondary objective was to determine the effectiveness of rasburicase in the control of hyperuricemia. RESULTS: Out of 50 patients, 25 reported a total of 76 treatment-emergent adverse events (TEAEs), including eight TEAEs of grade ≥ 3 in 12 patients. A drug-related serious AE was reported in one patient, and there was no incidence of death. The response rate in the intent-to-treat population was 100.0% (95% confidence interval 82.4-100.0) in patients (n = 19) with baseline uric acid level of > 8.0 mg/dL. Similarly, the response rate was 86.2% (n = 25) among 29 patients (60.4%) with baseline uric acid levels of ≤ 8.0 mg/dL. The maximum mean percentage decrease of plasma uric acid level in the overall patients was 96.9%. CONCLUSION: Rasburicase was well tolerated and effective in controlling hyperuricemia in Chinese pediatric patients with NHL and AL.

Influence of lipoproteins and antiplatelet agents on vein graft patency 1 year after coronary artery bypass grafting.

OBJECTIVE: It remains unclear whether aggressive low-density lipoprotein cholesterol (LDL-C) management (<1.8 mmol/L) can slow the process of vein graft stenosis. This study aimed to explore the impact of baseline LDL-C levels on vein graft patency in patients on ticagrelor with or without aspirin 1 year after coronary artery bypass grafting (CABG). METHODS: This was a post hoc analysis of the DACAB (Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery) trial (NCT02201771), a randomized controlled trial (ticagrelor + aspirin or ticagrelor vs aspirin) of patients undergoing CABG in China. The study subjects were stratified as LDL-low (baseline LDL-C <1.8 mmol/L, 148 patients with 430 vein grafts) versus LDL-high (baseline LDL-C ≥1.8 mmol/L, 352 patients with 1030 vein grafts). The primary outcome was the 1-year vein graft patency (Fitzgibbon grade A) assessed by coronary computed tomographic angiography or coronary angiography. RESULTS: Baseline/1-year LDL-C were 1.4/1.6 and 2.6/2.4 mmol/L in the LDL-low and LDL-high subgroups, respectively. Regardless of antiplatelet regimen, no significant inter-subgroup difference was observed for 1-year graft patency (LDL-low: 83.8% [359/430 grafts]; LDL-high: 82.3% [848/1030 grafts]; adjusted OR for non-patency [ORadj], 0.96; 95% confidence interval [CI], 0.62-1.50, P = .857). For both subgroups, the 1-year graft patency rates were greater with ticagrelor + aspirin versus aspirin (LDL-low: ORadj, 0.41; 95% CI, 0.17-0.97; LDL-high: ORadj, 0.38; 95% CI, 0.20-0.71; inter P = .679). CONCLUSIONS: In general, baseline LDL-C is not associated with 1-year vein graft patency after CABG. Regardless of the baseline LDL-C levels, ticagrelor + aspirin was superior to aspirin alone in maintaining vein graft patency. The primary factor causing early vein graft disease might not be atherosclerosis but thrombosis.

Lixisenatide is effective and safe as add-on treatment to basal insulin in Asian individuals with type 2 diabetes and different body mass indices: a pooled analysis of data from the GetGoal Studies.

INTRODUCTION: This analysis aims to investigate the efficacy and safety of once-daily lixisenatide add-on treatment to basal insulin in Asian individuals with type 2 diabetes, by baseline body mass index (BMI). RESEARCH DESIGN AND METHODS: Data from all Asian participants in the placebo-controlled GetGoal-Duo 1, GetGoal-L, and GetGoal-L-C Studies were pooled and categorized according to the following BMI subgroups:<25 kg/m2, 25-<30 kg/m2 and ≥30 kg/m2. Efficacy and safety of lixisenatide versus placebo were evaluated among BMI subgroups. Multivariable regression analyses were also conducted to explore the potential influence of BMI on efficacy outcomes after adjusting for baseline characteristics. RESULTS: 555 participants were included (mean age 53.9 years, 52.4% men). No significant differences in treatment effect between the BMI subgroups were observed for the changes from baseline to 24 weeks in glycated hemoglobin (HbA1c), fasting plasma glucose, postprandial glucose (PPG), PPG excursion, body weight, BMI, and basal insulin dose with lixisenatide, as well as the change in basal insulin dose at study endpoint and the proportion of participants achieving an HbA1c <7% at 24 weeks (all p values for interaction >0.15). In the multivariable regression analysis, participants in the lowest BMI group had a smaller reduction in body weight over the 24-week treatment period relative to the highest BMI group (p=0.023). CONCLUSIONS: This post hoc analysis indicates that lixisenatide improved glycemic control regardless of baseline BMI and was well tolerated in Asian individuals unable to achieve their HbA1c target on basal insulin±oral antidiabetic drugs.

Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T.

BACKGROUND: Combining an immune checkpoint inhibitor with a tumor vaccine may modulate the immune system to leverage complementary mechanisms of action that lead to sustained T-cell activation and a potent prolonged immunotherapeutic response in metastatic castration resistant prostate cancer (mCRPC). METHODS: Subjects with asymptomatic or minimally symptomatic mCRPC were randomly assigned in a 1:1 ratio to receive either atezolizumab followed by sipuleucel-T (Arm 1) or sipuleucel-T followed by atezolizumab (Arm 2). The primary endpoint was safety, while secondary endpoints included preliminary clinical activity such as objective tumor response and systemic immune responses that could identify key molecular and immunological changes associated with sequential administration of atezolizumab and sipuleucel-T. RESULTS: A total of 37 subjects were enrolled. The median age was 75.0 years, median prostate specific antigen (PSA) was 21.9 ng/mL, and subjects had a median number of three prior treatments. Most subjects (83.8%) had at least one treatment-related adverse event. There were no grade 4 or 5 toxicities attributed to either study drug. Immune-related adverse events and infusion reactions occurred in 13.5% of subjects, and all of which were grade 1 or 2. Of 23 subjects with Response Evaluation Criteria in Solid Tumors measurable disease, only one subject in Arm 2 had a partial response (PR) and four subjects overall had stable disease (SD) at 6 months reflecting an objective response rate of 4.3% and a disease control rate of 21.7%. T-cell receptor diversity was higher in subjects with a response, including SD. Immune response to three novel putative antigens (SIK3, KDM1A/LSD1, and PIK3R6) appeared to increase with treatment. CONCLUSIONS: Overall, regardless of the order in which they were administered, the combination of atezolizumab with sipuleucel-T appears to be safe and well tolerated with a comparable safety profile to each agent administered as monotherapy. Correlative immune studies may suggest the combination to be beneficial; however, further studies are needed. TRIAL REGISTRATION NUMBER: NCT03024216.

Efficacy of once-daily glucagon-like peptide-1 receptor agonist lixisenatide as an add-on treatment to basal insulin in Asian and white adults with type 2 diabetes mellitus: An individual-level pooled analysis of phase III studies.

AIMS/INTRODUCTION: The prevalence and pathophysiological background of type 2 diabetes mellitus vary across ethnicities, and can affect treatment responses. Adding lixisenatide to basal insulin (BI) in type 2 diabetes mellitus patients has shown improvements in glycated hemoglobin (HbA1c) and postprandial glycemic (PPG) excursions, without increasing hypoglycemic events. We aim to compare the efficacy of lixisenatide in Asian and white patients inadequately controlled with basal insulin. MATERIALS AND METHODS: An individual-level pooled analysis of two multi-national phase III studies, GetGoal-L and GetGoal-L-C, was carried out to assess the efficacy of lixisenatide versus placebo as an add-on treatment to BI ± metformin in Asian and white patients with type 2 diabetes mellitus. Change in HbA1c, 2-h PPG and PPG excursion were analyzed, along with possible predictors of glycemic control. RESULTS: Pooled data showed that baseline characteristics were similar between Asian and white patients with the exception of bodyweight, body mass index and BI dose being higher in white patients. After 24 weeks, lixisenatide reduced HbA1c in both ethnic groups, with no statistically significant difference between the two groups (Asian patients least squares mean difference -0.49, 95% confidence interval -0.68 to - 0.30 and white patients least squares mean difference -0.45, 95% confidence interval -0.63 to - 0.26; P = 0.6287). Similarly, no significant difference was found in 2-h PPG reduction between both groups (least squares mean difference for Asian vs white patients: -3.37 vs -3.93; P = 0.3203). Treatment with lixisenatide contributed to HbA1c reduction of -0.56% after adjustment of baseline HbA1c level in Asian patients, and -0.41% in white patients. CONCLUSIONS: Adding lixisenatide to BI significantly reduced HbA1c and 2-h PPG levels in both Asian and white participants with type 2 diabetes mellitus. No differences in treatment effect were observed between the two populations.

Annual glycemic variations and risk of cancer among Chinese patients with type 2 diabetes mellitus: A population-based cohort study in Shanghai.

BACKGROUND: Long-term glycemic variation in diabetes patients may have contributed to cancer incidence. AIM: In this study we aimed at the association between annual glycemic variation and the risk of cancer in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: Subjects of this study were from an established population-based cohort of T2DM patients in Minhang District of Shanghai, China. Incident cancer were obtained from the Shanghai Cancer Registry. Glycemic variation was evaluated using the annual fasting glucose coefficient of variation (FG-CV), which was used as a time-dependent variable in a Cox regression model to estimate the associations with the cancer risk. Restricted cubic splines were used to explore potential non-linear associations. RESULTS: A total of 2,140 incident cancers (1100 men and 1040 women) were identified from the 46,202 diabetes patients during 12-year follow-up. The annual FG-CV remained significantly associated with an increased risk of cancer, even after adjusting for the annual mean FG level. A significant non-linear association was found in male T2DM patients, and a significant linear association in female patients. CONCLUSIONS: The positive association of the annual FG-CV with the risk of cancer in T2DM patients indicate the importance to stabilize the FG level.

Autoantibody Landscape in Patients with Advanced Prostate Cancer.

PURPOSE: Autoantibody responses in cancer are of great interest, as they may be concordant with T-cell responses to cancer antigens or predictive of response to cancer immunotherapies. Thus, we sought to characterize the antibody landscape of metastatic castration-resistant prostate cancer (mCRPC). EXPERIMENTAL DESIGN: Serum antibody epitope repertoire analysis (SERA) was performed on patient serum to identify tumor-specific neoepitopes. Somatic mutation-specific neoepitopes were investigated by associating serum epitope enrichment scores with whole-genome sequencing results from paired solid tumor metastasis biopsies and germline blood samples. A protein-based immunome-wide association study (PIWAS) was performed to identify significantly enriched epitopes, and candidate serum antibodies enriched in select patients were validated by ELISA profiling. A distinct cohort of patients with melanoma was evaluated to validate the top cancer-specific epitopes. RESULTS: SERA was performed on 1,229 serum samples obtained from 72 men with mCRPC and 1,157 healthy control patients. Twenty-nine of 6,636 somatic mutations (0.44%) were associated with an antibody response specific to the mutated peptide. PIWAS analyses identified motifs in 11 proteins, including NY-ESO-1 and HERVK-113, as immunogenic in mCRPC, and ELISA confirmed serum antibody enrichment in candidate patients. Confirmatory PIWAS, Identifying Motifs Using Next-generation sequencing Experiments (IMUNE), and ELISA analyses performed on serum samples from 106 patients with melanoma similarly revealed enriched cancer-specific antibody responses to NY-ESO-1. CONCLUSIONS: We present the first large-scale profiling of autoantibodies in advanced prostate cancer, utilizing a new antibody profiling approach to reveal novel cancer-specific antigens and epitopes. Our study recovers antigens of known importance and identifies novel tumor-specific epitopes of translational interest.

Adherence to Dietary Recommendations among Long-Term Breast Cancer Survivors and Cancer Outcome Associations.

BACKGROUND: Adherence to dietary recommendations has been shown to be associated with reduced mortality in healthy populations. Little is known about the possible benefits of adherence to dietary recommendations among breast cancer survivors. METHODS: Dietary information was collected using food frequency questionnaires at the 5-year postdiagnosis survey in 3,450 5-year breast cancer survivors from the Shanghai Breast Cancer Survival Study. Adherence scores to Chinese Food Pagoda (CHFP)-2007, CHFP-2016, modified Dietary Approaches to Stop Hypertension (DASH), and Healthy Eating Index 2015 (HEI-2015) were created. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for total mortality and breast cancer-specific events according to adherence scores. RESULTS: Participants in the highest quartiles of CHFP-2007, CHFP-2016, and DASH had 25% to 34% lower risk of total mortality (HR, 0.66; 95% CI, 0.48-0.89 for CHFP-2007; HR, 0.75; 95% CI, 0.55-1.01 for CHFP-2016; HR, 0.66; 95% CI, 0.49-0.91 for DASH), and 36% to 40% lower risk of breast cancer-specific events (HR, 0.64; 95% CI, 0.44-0.93 for CHFP-2007; HR, 0.67; 95% CI, 0.45-0.99 for CHFP-2016; HR, 0.60; 95% CI, 0.40-0.90 for DASH) comparing with the lowest quartiles. Associations did not vary by known prognostic factors. HEI-2015 scores were not significantly associated with breast cancer outcomes. CONCLUSIONS: Higher adherence to CHFP and DASH dietary guidelines post-cancer diagnosis was associated with reduced risk of both overall death and breast cancer-specific recurrence or death among long-term breast cancer survivors. IMPACT: Our study highlights the importance of overall dietary quality among long-term breast cancer survivors.

Spatial Analysis of Built Environment Risk for Respiratory Health and Its Implication for Urban Planning: A Case Study of Shanghai.

Urban planning has been proven and is expected to promote public health by improving the built environment. With a focus on respiratory health, this paper explores the impact of the built environment on the incidence of lung cancer and its planning implications. While the occurrence of lung cancer is a complicated and cumulative process, it would be valuable to discover the potential risks of the built environment. Based on the data of 52,009 lung cancer cases in Shanghai, China from 2009 to 2013, this paper adopts spatial analytical methods to unravel the spatial distribution of lung cancer cases. With the assistance of geographic information system and Geo-Detector, this paper identifies certain built environments that are correlated with the distribution pattern of lung cancer cases in Shanghai, including the percentage of industrial land (which explains 28% of the cases), location factors (11%), and the percentages of cultivated land and green space (6% and 5%, respectively). Based on the quantitative study, this paper facilitates additional consideration and planning intervention measures for respiratory health such as green buffering. It is an ecological study to illustrate correlation that provides approaches for further study to unravel the causality of disease incidence and the built environment.

Body mass index and cancer risk among Chinese patients with type 2 diabetes mellitus.

BACKGROUND: Obesity and diabetes are two risk factors for cancer. To evaluate the association of body mass index (BMI) with cancer risk in diabetic patients may improve current understanding of potential mechanisms. METHODS: A retrospective cohort study was conducted in 51,004 newly diagnosed T2DM patients derived from an electronic health record (EHR) database of Minhang district in Shanghai, China. Incident cancer cases and all-cause deaths occurred before September 30, 2015 were identified by linking with the Shanghai Cancer Registry and the Shanghai Vital Statistics. To examine the potential non-linear and linear relationships of BMI and cancer risk, Cox proportional hazard models with and without restricted cubic spline functions were used, respectively. RESULTS: A non-linear association was observed between BMI and overall cancer incidence in men younger than 60 years old (p for non-linearity = 0.009). Compared with those having BMI of 25.0 kg/m2, the cancer risk increased in those with either lower or higher BMI. In women older than 60 years old, linear dose-response relationships were observed between BMI and the risk of both overall cancer and breast cancer. As each unit increase in BMI, the overall cancer risks elevated by 3% (95%CI: 1-5%) and the breast cancer risks increased by 7% (95%CI: 1-13%). No significant association was observed between BMI and other common cancer sites. CONCLUSIONS: Our results show that the effect of BMI on cancer risk in Chinese patients with T2DM may vary by gender, age and cancer subtypes, suggesting different underlying biological mechanisms.

Time-varying effects of prognostic factors associated with long-term survival in breast cancer.

The impact of some prognostic factors on breast cancer survival has been shown to vary with time since diagnosis. However, this phenomenon has not been evaluated in Asians. In the present study, 4886 patients were recruited from the Shanghai Breast Cancer Survival Study, a longitudinal study of patients diagnosed during 2002-2006, with a median follow-up time of 11.2 years. Cox model incorporating time-by-covariate interactions was used to describe the time-varying effects of prognostic factors related to overall survival and disease-free survival. Age ≥65 years showed a progressively negative effect on breast cancer prognosis over time, whereas tumour size >2 cm had a lasting and constant impact. Age significantly modified the effects of the tumour grade, nodal status and oestrogen receptor (ER) status on breast cancer survival. The detrimental effect of poorly differentiated tumours was time limited and more obvious in patients aged 45-54 years. Having ≥4 positive lymph nodes had a persistent and negative impact on prognosis, although it attenuated in later years; the phenomenon was more prominent in the 55-64-year age group. ER-positive status was protective in the first 3 years after diagnosis but was related to a higher risk of recurrence in later years; the time-point when ER-positive status turned into a risk factor was earlier in younger patients. These results suggest that older age, positive lymph node status, larger tumour size and ER-positive status are responsible for late death or recurrence in Asian breast cancer survivors. Extended endocrine therapy should be given earlier in younger ER-positive patients.

Body mass index, waist-to-hip ratio and late outcomes: a report from the Shanghai Breast Cancer Survival Study.

Obesity has been well studied in relation to breast cancer survival. However, the associations of post-diagnosis obesity and late outcomes (≥5 years after diagnosis) have been much less studied. A total of 4062 5-year disease-free patients were recruited from the Shanghai Breast Cancer Survival Study, a longitudinal study of patients diagnosed during 2002-2006. Cox proportional hazard model with restricted cubic spline were used to evaluate the potential non-linear associations of post-diagnosis body mass index (BMI) and waist-to-hip ratio (WHR) with late all-cause mortality and late recurrence. While no significant association was observed for post-diagnosis BMI or WHR with late recurrence; a U-shaped association was observed for the two measures with late all-cause death. Women with BMI of 25.0 kg/m2 or WHR of 0.83 were at the lowest risk of late all-cause mortality, whereas those with BMI beyond the range of 22.1-28.7 kg/m2 or WHR beyond the range of 0.81-0.86 had a higher risk. ER, stage or menopausal status did not modify the effect of post-diagnosis BMI or WHR on the outcomes. In conclusion, post-diagnosis BMI and WHR, as indicators of overall and central obesity respectively, were associated with late all-cause mortality in U-shaped pattern among long-term breast cancer survivors.

[Incidence trend of malignant tumors in children in Shanghai].

OBJECTIVE: To understand the incidence trend of malignant tumors in children aged <15 years in Shanghai. METHODS: The <15 years old children diagnosed with cancer in Shanghai between 2009 and 2011 were included in this study. The types of malignant tumors were classified according to International Classification of Childhood Cancer, Version 3 (ICCC-3). The gender and age specific incidences of malignant tumors were analyzed. Software Joinpoint was used to calculate the annual percentage of childhood cancer cases. RESULTS: A total of 460 cases of childhood cancer were diagnosed in Shanghai during 2009-2011, accounting for 0.3% of total cancer cases. The crude incidence was 129.0 per million and the age standardized rate (ASR) was 129.6 per million. The ASR was higher in boys (142.1 per million) than in girls (116.4 per million). The boy to girl ratio was 1.2(95%CI: 1.0-1.5). The incidence was highest in age group <5 years (165.1 per million). The incidences in age groups 5-9 years and 10-14 years were 101.2 per million and 113.9 per million, respectively. Leukemia was the most common cancer in children (n=165, 35.9%, ASR: 47.0 per million), followed by central nervous system tumors (n=91, 19.8%, ASR: 25.6 per million) and lymphomas (n=45, 9.8%, ASR: 12.6 per million). The age and gender specific incidence of malignant tumors and the type specific incidence of malignant tumors in children in Shanghai had no significant changes during the study period. CONCLUSIONS: The incidence of malignant tumors was higher in boys than in girls in Shanghai. Leukemia, central nervous system tumors and lymphomas were the three most common cancers in children. The overall incidence of malignant tumors in children in Shanghai had no significant changes during 2002-2011.

[Disparities of breast cancer burden between China and western countries and its implication].

The disease burden of breast cancer in China is growing, and its proportion contributed to the global burden is increasing accordingly. The western countries have achieved reduction of mortality and slow growth of incidence, while the breast cancer incidence and mortality rates have been increasing constantly with lower survival rates in China. The remarkable characteristics of breast cancer burden in China is the disparities of the current status and time trends of incidence, mortality and survival between urban and rural area. The breast cancer disease distributions and time trends in China and the differential from the developed countries are described, which may be benefit to draw the international experience on prevention, early detection, medical care and survival management. Assessment of the existing evidence, elaboration of the prevention, control strategies in consideration of Chinese social-economic and culture situation would be beneficial to rise to the future challenge.

[Long-term survival analysis of different breast cancer molecular subtypes: Shanghai Breast Cancer Survival Study].

OBJECTIVES: To analyze the survival of breast cancer molecular subtypes and to examine the effect of therapy on the long-term prognosis of different subtypes. METHODS: This study included 3 586 breast cancer patients with estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) information in Shanghai Breast Cancer Survival Study, a population-based prospective cohort study established in 2002. Molecular subtypes, based on immunohistochemistry were categorized as follows: Luminal A, Luminal B, HER2, and triple-negative subtype. Characteristics and clinical data were collected through questionnaires and medical records at baseline survey and sequential follow-up surveys. Survival rates of different molecular subtypes were analyzed and compared with Log-rank tests. Multiple Cox regression models were used to evaluate the effect of therapy on long-term prognosis of different molecular subtypes. RESULTS: Among the 3 586 cases, Luminal A, Luminal B, HER2 and triple-negative breast cancer subtypes accounted for 54.5%, 16.6%, 13.9%, and 14.9%, respectively. With a median follow-up of 10.3 years (ranging 0.6 to 12.8 years), the 10-year overall survival (OS) rates for the four subtypes were 82.7% (95% CI: 80.9% to 84.4%), 77.7% (95% CI: 74.1% to 80.8%), 76.3% (95% CI: 72.3% to 79.8%), and 74.8% (95% CI: 70.9% to 78.3%), respectively. The 10-year disease to free survival (DFS) rates were 79.0% (95% CI: 76.7% to 81.0%), 76.0% (95% CI: 71.9% to 79.5%), 73.6% (95% CI: 68.9% to 77.7%), and 74.5% (95% CI: 69.4% to 78.9%), respectively. Significant difference in survival among four subtypes was observed (Log-rank test, P<0.01). Multivariate Cox regression indicated that hormonal therapy can significantly reduce the long-term risk of total mortality and recurrence breast cancer specific mortality among Luminal A subtype patients. Adjuvant chemotherapy could improve the long-term prognosis of triple-negative breast cancer. No benefit from radiotherapy was observed for four subtypes of breast cancer in terms of long-term prognosis. CONCLUSIONS: Molecular subtypes based on ER/PR/HER2 could provide important information to predict breast cancer prognosis. The hormonal status was an important basis for individualized therapy and precision medicine.

Prediction and analysis of the protein interactome in Pseudomonas aeruginosa to enable network-based drug target selection.

Pseudomonas aeruginosa (PA) is a ubiquitous opportunistic pathogen that is capable of causing highly problematic, chronic infections in cystic fibrosis and chronic obstructive pulmonary disease patients. With the increased prevalence of multi-drug resistant PA, the conventional "one gene, one drug, one disease" paradigm is losing effectiveness. Network pharmacology, on the other hand, may hold the promise of discovering new drug targets to treat a variety of PA infections. However, given the urgent need for novel drug target discovery, a PA protein-protein interaction (PPI) network of high accuracy and coverage, has not yet been constructed. In this study, we predicted a genome-scale PPI network of PA by integrating various genomic features of PA proteins/genes by a machine learning-based approach. A total of 54,107 interactions covering 4,181 proteins in PA were predicted. A high-confidence network combining predicted high-confidence interactions, a reference set and verified interactions that consist of 3,343 proteins and 19,416 potential interactions was further assembled and analyzed. The predicted interactome network from this study is the first large-scale PPI network in PA with significant coverage and high accuracy. Subsequent analysis, including validations based on existing small-scale PPI data and the network structure comparison with other model organisms, shows the validity of the predicted PPI network. Potential drug targets were identified and prioritized based on their essentiality and topological importance in the high-confidence network. Host-pathogen protein interactions between human and PA were further extracted and analyzed. In addition, case studies were performed on protein interactions regarding anti-sigma factor MucA, negative periplasmic alginate regulator MucB, and the transcriptional regulator RhlR. A web server to access the predicted PPI dataset is available at http://research.cchmc.org/PPIdatabase/.

[Estimates and prediction on incidence, mortality and prevalence of breast cancer in China, 2008].

OBJECTIVE: To estimate the incidence, mortality and 5-year prevalence of breast cancer in China, in 2008. METHODS: Data from 36 cancer registries and the Third National Death Survey in China (2004 - 2005) were used to estimate the incidence, mortality and 5-year prevalence of breast cancer in China in 2008. Mathematical models were used to predict the breast cancer incidence and mortality in the next 20 years. RESULTS: In 2008, the incidence of breast cancer was 169 452 (14.2%) with the incidence rate of 21.6/100 000, ranking the second among all the cancers. Deaths due to breast cancer was 44 908 (6.1%) with mortality as 5.7/100 000, which ranked the sixth among all the cancers. The 5-year prevalence rate of breast cancer in China was 120.8/100 000, taking up the proportion as 26.1%, ranking the first among all the cancers. Breast cancer was seen more frequently among people aged between 40 to 70. Our data on prediction showed that the incidence and mortality of breast cancer in China would gradually increase in the next 20 years. CONCLUSION: Breast cancer was the second cause of incidence rates among all the cancers in China, with both increasing incidence and mortality. Population at most risk for breast cancer were those aged 40 to 70, who deserved special programs for prevention and control.

[Estimates and prediction of prostate cancer incidence, mortality and prevalence in China, 2008].

OBJECTIVE: To estimate the incidence, mortality and 5-year prevalence of prostate cancer in China, in 2008. METHODS: Data from 36 cancer registries and the Third National Death Survey in China (2004-2005) was used to estimate the incidence, mortality and 5-year prevalence rates of prostate cancer in China in 2008. Mathematical models were used to predict the incidence and mortality of prostate cancer in the next 20 years. RESULTS: In 2008, the incidence of prostate cancer was 33 802 (2.1%), with the incidence rate as 4.3/100 000, which ranked the eighth among all the male cancers. Mortality of prostate cancer in China was 14 297 (1.2%) with the mortality rate of 1.8/100 000, which ranked eleventh among all the male cancers. The 5-year prevalence rate of prostate cancer in China was 75 535 (3.5%) with the proportion of 13.8/100 000, ranking the seventh among all the male cancers. The incidence and mortality of prostate cancer in men before the age of 60 maintained at a low level, but rose rapidly after the age of 60. Data on prediction showed that the incidence and mortality of prostate cancer in China would gradually increase in the next 20 years. CONCLUSION: Both incidence and mortality of prostate cancer in China would keep increasing in the future. Prevention and control programs for prostate cancer should be strengthened.