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BackgroundHigh levels of circulating estradiol (E2) are associated with increased risk of breast cancer, whereas its relationship with breast cancer prognosis is still unclear. We studied the effect of E2 concentration on breast cancer survival among pre- menopausal and post- menopausal patients in China.MethodsWe evaluated this association among 8766 breast cancer cases diagnosed between 2005 and 2017 from the Tianjin Breast Cancer Cases Cohort. Levels of serum E2 were measured in pre-menopausal and post-menopausal women. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between quartile of E2 levels and overall survival (OS) and progression-free survival (PFS) of breast cancer. The penalized spline was then used to test for non-linear relationships between E2 (continuous variable) and survival endpoints.ResultsA total of 612 deaths and 982 progressions occurred over follow-up through 2017. Compared to women in the quartile 3, the highest quartile of E2 was associated with reduced risk of both PFS in pre-menopausal women (HR=1.79, 95% CI: 1.17-2.75, P=0.008) and OS in post-menopausal women (HR=1.35, 95% CI: 1.04-1.74, P=0.023). OS and PFS in pre-menopausal women exhibited a nonlinear relation (“L-shaped” and “U-shaped”, respectively) with E2 levels. However, there was a linear relationship in post-menopausal women, among whom increasing E2 was associated with escalating risks of death and progression. Moreover, patients with estrogen receptor-negative (ER-negative) breast cancer showed a “U-shaped” relationship with OS and PFS in pre-menopausal women.ConclusionsPre-menopausal breast cancer patients have a plateau stage of prognosis at the intermediate concentrations of E2, whereas post-menopausal patients have no apparent threshold, and ER status may have an impact on this relationship.

Lung cancer is the leading cause of cancer death worldwide. Data on the effectiveness of one-off low-dose CT (LDCT) in reducing lung cancer mortality and all-cause mortality are needed to inform screening programmes in countries with limited medical resources. We aimed to evaluate the effectiveness of one-off LDCT screening in the early detection of lung cancer in China.A multicentre, population-based, prospective cohort study was done in 12 cities of eight provinces across China, recruiting individuals aged 40-74 years who were asymptomatic for lung cancer with no lung cancer history. Participants were classified as at high risk or low risk of lung cancer using a sex-specific risk score that incorporated cigarette smoking, level of physical activity, occupational exposures, history of chronic respiratory diseases, family history of lung cancer, diet, and passive smoking (women only). Participants at high risk were invited for a one-off LDCT scan and were classified into screened and non-screened groups on the basis of whether or not they had the scan. Lung cancer incidence density, lung cancer mortality, and all-cause mortality were calculated for the screened and non-screened groups. The effectiveness of a one-off LDCT scan was evaluated by a comparison of the screened and non-screened groups in terms of lung cancer mortality and all-cause mortality in the period from cohort entry until administrative censoring (June 20, 2020). Inverse probability weighting was adopted to account for potential imbalanced factors between the two groups and Cox proportional hazards model was used to estimate the weighted associations between mortality and one-off LDCT scans.Between Feb 19, 2013, and Oct 31, 2018, 1 032 639 individuals were assessed for eligibility. 1 016 740 participants were enrolled in the study, of whom 3581 had a lung cancer diagnosis after a median follow-up of 3·6 years (IQR 2·8-5·1). Among the 223 302 participants at high risk, 79 581 (35·6%) had an LDCT scan (screened group) and 143 721 (64·4%) did not (non-screened group). After inverse probability weighting, lung cancer incidence density was 47·0% higher (hazard ratio 1·47 [95% CI 1·27-1·70]; p0·0001), lung cancer mortality was 31·0% lower (0·69 [95% CI 0·53-0·92]; p=0·010) and all-cause mortality was 32·0% lower (0·68 [0·57-0·82]; p0·0001) for participants in the screened group compared with those in the non-screened group.One-off LDCT screening was associated with significantly lower lung cancer mortality and all-cause mortality in a large population in China. Our results point to the promise of one-off LDCT screening in countries with limited medical resources. Further studies are needed to explore interactions by subgroup-including sex, age, smoking status, and economic status-to develop population-specific screening strategies.Ministry of Finance and National Health Commission of the People's Republic of China.For the Chinese translation of the abstract see Supplementary Materials section.

Background Patients with spinal cord injury (SCI) often present with different degrees of neuropathic pain (NP). Glia-mediated inflammatory response plays a key role. The transient receptor potential vanilloid subtype 1 (TRPV1), as an ion channel receptor closely related to pain, plays an important role in NP, although its mechanism remains unclear. We explored the role of TRPV1 in NP after SCI and its effect on the proliferation and activation of C-X3-C motif chemokine ligand 1 (CX3CL1)-positive glial cells. Methods The SCI rat model was established using the modified Allen’s spinal cord injury model. After SCI, rats in each group were administered the TRPV1 antagonist SB705498 (10 mg/kg) or 2 mL of vehicle intragastrically for 7 consecutive days. The hindlimb motor function of rats after injury was assessed by the Basso, Beattie, and Bresnahan rating scale; Von Frey fibres and plantar thermal stimulation were used to evaluate the changes in rats’ mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL), respectively; haematoxylin and eosin staining, double immunofluorescent staining, and Western blotting were used to investigate the role of TRPV1 in NP after SCI and its effect on the proliferation and activation of CX3CL1-positive glial cells. Results The chemokine CX3CL1 was mainly expressed in the dorsal horn neurons of the spinal cord and also to a certain extent in microglia, astrocytes, and oligodendrocytes after SCI. The expression of TRPV1 and CX3CL1 in the dorsal horn of the spinal cord in rats was significantly upregulated, and the PWT and PWL of rats were significantly decreased after SCI. The TRPV1 antagonist not only inhibited the activation of TRPV1, but also significantly inhibited the apoptosis of neurons and oligodendrocytes and proliferation and activation of inflammation-related CX3CL1-positive glial cells induced by SCI. Conclusion These results suggest that TRPV1 is involved in the occurrence and development of NP after SCI in rats by mediating the proliferation and activation of CX3CL1-positive glial cells in the dorsal horn of the spinal cord; inhibition of TRPV1 activity attenuates the proliferation and activation of CX3CL1-positive glial cells, thereby reducing symptoms of central sensitisation.

Objective: To develop and evaluate the screening performance of a low-cost high-risk screening strategy for breast cancer in low resource areas. Methods: Based on the Multi-modality Independent Screening Trial, 6 questionnaire-based risk factors of breast cancer (age at menarche, age at menopause, age at first live birth, oral contraceptive, obesity, family history of breast cancer) were used to determine the women with high risk of breast cancer. The screening performance of clinical breast examination (CBE), breast ultrasonography (BUS), and mammography (MAM) were calculated and compared to determine the optimal screening method for these high risk women. Results: A total of 94 breast cancers were detected among 31,720 asymptomatic Chinese women aged 45–65 years. Due to significantly higher detection rates (DRs) and suitable coverage of the population, high risk women were defined as those with any of 6 risk factors. Among high risk women, the DR for BUS [3.09/1,000 (33/10,694)] was similar to that for MAM [3.18/1,000 (34/10,696)], while it was significantly higher than that for the CBE [1.73/1,000 (19/10,959), P = 0.002]. Compared with MAM, BUS showed significantly higher specificity [98.64% (10,501/10,646) vs. 98.06% (10,443/10,650), P = 0.001], but no significant differences in sensitivity [68.75% (33/48) vs. 73.91% (34/46)], positive prediction values [18.54% (33/178) vs. 14.11% (34/241)], and negative prediction values [99.86% (10,501/10,516) vs. 99.89% (10,443/10,455)]. Further analyses showed no significant difference in the percentages of early stage breast cancer [53.57% (15/28) vs. 50.00% (15/30)], lymph node involvement [22.73% (5/22) vs. 28.00% (7/25)], and tumor size ≥ 2 cm [37.04% (10/27) vs. 29.03% (9/31)] between BUS and MAM. Subgroup analyses stratified by breast densities or age at enrollment showed similar results. Conclusions: The low-cost high-risk screening strategy based on 6 questionnaire-based risk factors was an easy-to-use method to identify women with high risk of breast cancer. Moreover, BUS and MAM had comparable screening performances among high risk women.

Background: Previous studies investigated the instability of molecular subtype markers [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)] in several clinical settings, but not for second primary breast cancer (SPBC) after first primary breast cancer (FPBC). Methods: A total of 15,390 patients with SPBC were preliminarily selected from the Surveillance, Epidemiology, and End Results Program, and 3,777 patients with complete information on three molecular subtype markers in both FPBC and SPBC were included in the final analyses. The instability of molecular subtype markers and their prognostic implications and potential influential factors were well investigated.Results: The overall instability rates of ER, PR, and HER2 between FPBC and SPBC were 23.0%, 35.0%, and 18.3%, respectively. Gains of ER, PR, and HER2 after negative index markers were 48.7%, 37.9% and 11.5%, while losses of markers after positive index markers were 16.6%, 33.8% and 56.7%. Loss of ER was significantly associated with increased mortality (18.1% vs. 7.9%, PP of PR status. However, loss of HER2 was significantly associated with decreased mortality (8.7% vs. 16.3%, P=0.014), and no significant association was observed between the gain of HER2 and the prognosis of SPBC. Multivariate competing risk analyses showed similar results. HER2 status in FPBC, chemotherapy, and radiotherapy was significantly associated with instability of ER/PR (all PConclusion: Instability of molecular subtype markers is observed in a considerable proportion of patients and has statistically significant prognostic implications. Biopsies should be taken as a routine procedure for better therapy management.

Scene text detection has become an important research topic. It can be broadly applied to much industrial equipment, such as smart phones, intelligent scanners, and IoT devices. Many existing scene text detection methods have achieved advanced performance. However, text in scene images is presented with differing orientations and varying shapes, rendering scene text detection a challenging task. This paper proposes a method for detecting texts in scene images. First, four stages of low-level features is extracted using DenseNet121. Low-level features are then merged by transposed convolution and skip connection. Second, the merged feature map is used to generate a score map, box map, and angle map. Finally, the Locality-Aware Non-Maximum Suppression (LANMS) is applied as post-processing to generate the final bounding box. The proposed method achieves an F-measure of 0.826 on ICDAR 2015 and 0.761 on MSRA-TD500, respectively.

Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to cancer prognosis. Here we performed a two-stage study of 2647 breast cancer patients to explore the association between SNPs within microRNA binding sites and breast cancer prognosis. In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs associated with breast cancer prognosis in another dataset using the TaqMan platform. We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (P

Background: Inflammatory markers have been reported to be predictors for the presence of epithelial ovarian cancer (EOC), however, the cut-off value of each marker remains unclear and predictive capability of the markers in different histology types of EOC is still unknown. Methods: A total of 207 patients with benign ovarian masses and 887 EOC patients who underwent surgical resection, and were pathologically diagnosed were included. We compared the difference of preoperative inflammatory markers between benign ovarian masses and EOC patients. Stratified analysis by histology subtype was further conducted. Logistic regression analyses and receiver operating characteristic (ROC) curves was used to evaluate the predictive capability of the markers. Results: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were significantly associated with all stages and subtypes of EOC (P

Background: Risk prediction models integrating classical risk factors (CRF), mammographic density (MD), and polygenic risk score (PRS) are increasingly developed to identify high-risk groups of breast cancer. Few studies investigate the screening performance in high-risk groups by these models.Methods: Based on a median follow-up of 11.7 years of 7794 women from the Multi-modality Independent Screening Trial (MIST), four risk prediction models with CRF (ModelCRF), CRF and MD (ModelCRF+MD), CRF and PRS (ModelCRF+PRS), and all three components (ModelFULL) were developed to identify high-risk groups of breast cancer. The hazard ratio (HR) and 95% confidential interval (CI) of breast-cancer mortality for high-risk groups compared to low-risk groups was calculated to determine potential benefit of risk-reducing interventions. The detection rate (DR), accuracy and cancer-stage for clinical breast examination (CBE), breast ultrasonography (BUS), and mammography (MAM) were compared to determine the optimal screening method for high-risk groups.Results: The areas under the curve of risk prediction model increased from 0.573 (95%CI: 0.532-0.614) for ModelCRF, to 0.587 (95%CI: 0.544-0.630) for ModelCRF+MD, 0.670 (95%CI: 0.622-0.717) for ModelCRF+PRS and 0.674 (95%CI: 0.623-0.725) for ModelFULL. The HRs of breast cancer mortality for high-risk groups compared to low-risk groups increased from 1.81 (95%CI: 1.17-2.81) for ModelCRF, to 2.22 (95%CI: 1.35-3.67) for ModelCRF+MD, 2.48 (95%CI: 1.43-4.29) for ModelCRF+PRS, and 3.68(95%CI: 1.94-6.99) for ModelFULL. Among high-risk groups by ModelCRF, the DR of BUS was similar to that of MAM (3.926/1,000 vs. 2.399/1,000, P=0.193), but significantly higher than that of CBE (1.091/1,000, P=0.024). Compared with MAM, BUS showed significantly lower sensitivity (50.0% vs. 81.8%, P=0.026), but comparable specificity (99.2% vs. 99.3%), positive prediction values (22.9% vs. 34.6%), and negative prediction values (99.8% vs. 99.9%). Further analyses showed no significant difference in the proportions of early-stage breast cancer detected between BUS and MAM (50.00% vs. 61.54%, P=0.673). Similar results were observed in high-risk groups by other models.Conclusions: Accurate risk assessment integrating CRF, MD and PRS is needed to identify high-risk groups of breast cancer. The higher the risk, the greater the benefit of the intervention. BUS was comparable to MAM for screening breast cancer in high-risk groups.

Background Most previous studies have focused more on the short-term risk of cardiovascular death related to traumatic psychological stress after cancer diagnosis, but less on the long-term risk of cardiovascular death. Recent studies suggested that the risk of cardiovascular death would probably outweigh the risk of index cancer death among long-time cancer survivors. However, it has not received enough attention. Methods Temporal trends in the proportions of cardiovascular death (PCV), cancer death (PCA), and other causes in all-cause deaths were used to show preliminary relationships between three causes of death in 4,806,064 cancer patients from the SEER Program. Competing mortality risk curves were used to investigate when cumulative cardiovascular mortality rate (CMRCV) began to outweigh cumulative cancer mortality rate (CMRCA) for cancer patients survived more than 10 years. Competing risk models were used to investigate independent factors associated with cardiovascular death in long-time cancer survivors. Results For all cancer patients, the PCV increased from 22.8% in the 5th year after cancer diagnosis, to 31.0% in 10th year, and 35.7% in the 20th year, while the PCA decreased from 57.7%, to 41.2% and 29.9%, respectively. The PCV outweighed the PCA (34.6% vs. 34.1%) since the 15th year for all cancer patients, as early as the ninth year for colorectal cancer patients (37.5% vs. 33.2%), and as late as the 22nd year for breast cancer patients (33.5% vs. 30.6%). The CMRCV outweighed CMRCA since the 15th year for cancer patients survived more than 10 years, the 5th year for those survived more than 15 years, and the 1st for those survived more than 20 years. Among cancer patients survived more than 20 years, elder age at diagnosis, male, local metastasis, and radiotherapy were associated with increased risk of cardiovascular death, while surgery and chemotherapy were associated with decreased risk of cardiovascular death. Sensitivity analysis by cancer sites showed similar results. Conclusions Cardiovascular death will gradually outweigh cancer death as survival time increases for most cancer patients. Cardio-oncologist should be involved as early as possible in the anti-cancer treatments to reduce cardiovascular death in long-term cancer survivors.

The burden of breast cancer has grown rapidly in China during recent decades. However, the association between tumor markers (CA15-3, CA125, and CEA) and breast cancer survival among certain molecular subtypes is unclear; we described this association in a large, population-based study. We conducted a cohort study including 10,836 women according to the Tianjin Breast Cancer Cases Cohort. Demographic and epidemiologic data were collected by a structured face-to-face questionnaire. Clinico-pathological parameters were abstracted from medical records, and follow-up information was obtained once a year by telephone. The primary endpoints were breast cancer-specific survival (BCSS) and disease-free survival (DFS). We utilized the Cox proportional hazard model to calculate hazard ratios (HRs) and 95% confidence intervals (CI). Among all patients, elevated CA15-3 and CEA exhibited consistently and statistically significant reduced BCSS compared with normal ones (CA15-3: HR 1.54, 95% CI 1.01–2.34; CEA: HR 2.45, 95% CI 1.40–4.30). Similar patterns of association were observed for DFS (CA15-3: HR 2.09, 95% CI 1.44–3.02; CEA: HR 2.71, 95% CI 1.71–4.27). Moreover, in luminal A subtype, high CA15-3 and CEA levels were associated with decreased BCSS (CA15-3: HR 4.47, 95% CI 2.04–9.81; CEA: HR 3.79, 95% CI 1.68–8.55) and DFS (CA15-3: HR 4.06, 95% CI 2.29–7.18, CEA: HR 3.41, 95% CI 1.75–6.64). In basal-like subtype, elevated CEA conferred reduction for BCSS (HR 5.13, 95% CI 1.65–15.9). However, no association was observed between CA125 and breast cancer outcome. Preoperative CA15-3 and CEA levels differ in breast cancer molecular subtypes and yield strong prognostic information in Chinese women with breast cancer. Measuring CA15-3 and CEA levels before surgery may have the potential in predicting breast cancer survival and offering patients’ personalized treatment strategy among luminal A and basal-like subtypes.

Objective To redefine overdiagnosis and reestimate the proportion of overdiagnosis of breast cancer caused by screening based on the Surveillance, Epidemiology, and End Results (SEER, 1973−2015) Program data. Methods The breast cancer diagnosed before 1977 was defined as the no-screening cohort since America had initiated breast cancer screening from 1977. The breast cancer diagnosed in 1999 was defined as the screening cohort due to no increases in both the proportion of early-stage breast cancer until 1999 and the overall survival of early-stage breast cancer diagnosed over the three years since 1999. The magnitude of overdiagnosis was calculated as the difference in the proportions of early-stage breast cancer patients with long-time (15-year) survival to all breast cancer patients between two cohorts. Results Over 23 years before and after widespread screening in America, the proportion of early-stage breast cancer patients increased from 52.1% (16,891/32,443) to 72.7% (16,021/22,025) (P

Purpose We aim to construct a nomogram to predict breast cancer survival and guide postoperative adjuvant chemotherapy in China. Patients and methods A total of 5,504 breast cancer patients from the Tianjin Breast Cancer Cases Cohort were included. Multivariable Cox regression was used to investigate the factors associated with overall survival (OS) and a nomogram was constructed based on these prognostic factors. The nomogram was internal and external validated and the performance was evaluated by area under the curve (AUC) and calibration curve. The partial score was also constructed and stratified them into low, moderate and high-risk subgroups for death according to the tripartite grouping method. Multivariate Cox regression analysis and the propensity score matching method were respectively used to test the association between adjuvant chemotherapy and OS in different risk subgroups. Results Age, diameter, histological differentiation, lymph node metastasis, estrogen, and progesterone receptor were incorporated into the nomogram and validation results showed this nomogram was well-calibrated to predict the 3-year [AUC =74.1%; 95% confidence interval (CI): 70.1-78.0%] and 5-year overall survival [AUC =72.3%; 95% CI: 69.6-75.1%]. Adjuvant chemotherapy was negatively associated with death in high risk subgroup [Hazard Ratio (HR) = 0.54; 95% CI: 0.37-0.77; P

Objective: The number of immediate breast reconstruction (IBR) procedures has been increasing in China. This study aimed to investigate the oncological safety of IBR, and to compare the survival and surgical outcomes between implant-based and autologous reconstruction. Methods: Data from patients diagnosed with invasive breast cancer who underwent immediate total breast reconstruction between 2001 and 2016 were retrospectively reviewed. Long-term breast cancer-specific survival (BCSS), disease-free survival (DFS), and locoregional recurrence-free survival (LRFS) were evaluated. Patient satisfaction with the breast was compared between the implant-based and autologous groups. BCSS, DFS, and LRFS were compared between groups after propensity score matching (PSM). Results: A total of 784 IBR procedures were identified, of which 584 were performed on patients with invasive breast cancer (implant-based, n = 288; autologous, n = 296). With a median follow-up of 71.3 months, the 10-year estimates of BCSS, DFS, and LRFS were 88.9% [95% confidence interval (CI) (85.1%–93.0%)], 79.6% [95% CI (74.7%–84.8%)], and 94.0% [95% CI (90.3%–97.8%)], respectively. A total of 124 patients completed the Breast-Q questionnaire, and no statistically significant differences were noted between groups (P = 0.823). After PSM with 27 variables, no statistically significant differences in BCSS, DFS, and LRFS were found between the implant-based (n = 177) and autologous (n = 177) groups. Further stratification according to staging, histological grade, lymph node status, and lymph-venous invasion status revealed no significant survival differences between groups. Conclusions: Both immediate implant-based and autologous reconstruction were reasonable choices with similar long-term oncological outcomes and patient-reported satisfaction among patients with invasive breast cancer in China.

OBJECTIVE: To evaluate the efficiency of low-dose computed tomography (LDCT) screening for lung cancer in China by analyzing the baseline results of a community-based screening study accompanied with a meta-analysis.METHODS: A first round of community-based lung cancer screening with LDCT was conducted in Tianjin, China, and a systematic literature search was performed to identify LDCT screening and registry-based clinical studies for lung cancer in China. Baseline results in the community-based screening study were described by participant risk level and the lung cancer detection rate was compared with the pooled rate among the screening studies. The percentage of patients per stage was compared between the community-based study and screening and clinical studies.RESULTS: In the community-based study, 5523 participants (43.6% men) underwent LDCT. The lung cancer detection rate was 0.5% (high-risk, 1.2%; low-risk, 0.4%), with stage I disease present in 70.0% (high-risk, 50.0%; low-risk, 83.3%), and the adenocarcinoma present in 84.4% (high-risk, 61.5%; low-risk, 100%). Among all screen-detected lung cancer, women accounted for 8.3% and 66.7% in the high- and low-risk group, respectively. In the screening studies from mainland China, the lung cancer detection rate 0.6% (95 %CI: 0.3%-0.9%) for high-risk populations. The proportions with carcinoma in situ and stage I disease in the screening and clinical studies were 76.4% (95 %CI: 66.3%-85.3%) and 15.2% (95 %CI: 11.8%-18.9%), respectively.CONCLUSIONS: The stage shift of lung cancer due to screening suggests a potential effectiveness of LDCT screening in China. Nearly 70% of screen-detected lung cancers in low-risk populations are identified in women.

The aims of the present study were to clarify the prognostic value of peripheral blood variables in patients with pancreatic ductal adenocarcinoma (PDAC), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), and to determine the association between these variables and S100 calcium-binding protein A4 (S100A4) expression in tumor tissue, which is another prognostic factor for PDAC. Patients with PDAC were recruited at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) between December 2008 and December 2014. A retrospective analysis was performed based on the recorded pre-treatment hematological parameters and clinical data. The prognostic value of NLR, PLR and LMR was examined. The association between these variables and S100A4 tissue expression was analyzed. Descriptive statistics and χ2 analyses were used in the present study. The median overall survival (OS) time of patients with PDAC was 9 months (range, 1-32 months). Univariate analysis revealed that NLR, LMR, carbohydrate antigen 19-9, surgery, chemotherapy, stage at diagnosis, tumor grade and age significantly affected OS. Although PLR exhibited no significant effects on OS, NLR and LMR were independent prognostic factors according to the multivariate analysis. Unpaired Student's t-test revealed differences between S100A4 expression and NLR, PLR and LMR. The results of the present study indicated that low NLR and high LMR were associated with a favorable prognosis in patients with PDAC. As a simply obtained and widely available index at diagnosis, NLR and LMR may become a novel predictive and classifying marker for PDAC in the clinical setting.

Objective: European lung cancer screening studies using computed tomography (CT) have shown that a management protocol based on measuring lung nodule volume and volume doubling time (VDT) is more specific for early lung cancer detection than a diameter-based protocol. However, whether this also applies to a Chinese population is unclear. The aim of this study is to compare the diagnostic performance of a volume-based protocol with a diameter-based protocol for lung cancer detection and optimize the nodule management criteria for a Chinese population.Methods: This study has a population-based, prospective cohort design and includes 4000 participants from the Hexi district of Tianjin, China. Participants will undergo low-dose chest CT at baseline and after 1 year. Initially, detected lung nodules will be evaluated for diameter and managed according to a routine diameter-based protocol (Clinical Practice Guideline in Oncology for Lung Cancer Screening, Version 2.2018). Subsequently, lung nodules will be evaluated for volume and management will be simulated according to a volume-based protocol and VDT (a European lung nodule management protocol). Participants will be followed up for 4 years to evaluate lung cancer incidence and mortality. The primary outcome is the diagnostic performance of the European volume-based protocol compared to diameter-based management regarding lung nodules detected using low-dose CT.Results: The diagnostic performance of volume- and diameter-based management for lung nodules in a Chinese population will be estimated and compared.Conclusions: Through the study, we expect to improve the management of lung nodules and early detection of lung cancer in Chinese populations.

Background Flavonoids seem to have hormone-like and anti-hormone properties so that the consumption of flavonoids may have potential effects on hormone-related cancers (HRCs), but the findings have been inconsistent so far. This meta-analysis was aimed to explore the association between flavonoids intake and HRCs risk among observational studies. Methods Qualified articles, published on PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) from January 1999 to March 2022 and focused on relationships between flavonoids (total, subclass of and individual flavonoids) and HRCs (breast, ovarian, endometrial, thyroid, prostate and testicular cancer), were retrieved for pooled analysis. Random effects models were performed to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Funnel plots and Begg’s/Egger’s test were used to evaluate the publication bias. Subgroup analyses and sensitivity analyses were conducted to explore the origins of heterogeneity. Results All included studies were rated as medium or high quality. Higher consumption of flavonols (OR = 0.85, 95% CI: 0.76–0.94), flavones (OR = 0.85, 95% CI: 0.77–0.95) and isoflavones (OR = 0.87, 95% CI: 0.82–0.92) was associated with a decreased risk of women-specific cancers (breast, ovarian and endometrial cancer), while the higher intake of total flavonoids was linked to a significantly elevated risk of prostate cancer (OR = 1.11, 95% CI: 1.02–1.21). A little evidence implied that thyroid cancer risk was augmented with the higher intake of flavones (OR = 1.24, 95% CI: 1.03–1.50) and flavanones (OR = 1.31, 95% CI: 1.09–1.57). Conclusions The present study suggests evidence that intake of total flavonoids, flavonols, flavones, flavanones, flavan-3-ols and isoflavones would be associated with a lower or higher risk of HRCs, which perhaps provides guidance for diet guidelines to a certain extent. Trial registration This protocol has been registered on PROSPERO with registration number CRD42020200720.

Background Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are caused by coronaviruses and have infected people in China and worldwide. We aimed to investigate whether COVID-19 and SARS exhibited similar spatial and temporal features at provincial level in mainland China. Methods The number of people infected by COVID-19 and SARS were extracted from daily briefings on newly confirmed cases during the epidemics, as of Mar. 4, 2020 and Aug. 3, 2003, respectively. We depicted spatiotemporal patterns of the COVID-19 and SARS epidemics using spatial statistics such as Moran’s I and the local indicators of spatial association (LISA). Results Compared to SARS, COVID-19 had a higher overall incidence. We identified 3 clusters (predominantly located in south-central China; the highest RR = 135.08, 95% CI: 128.36–142.08) for COVID-19 and 4 clusters (mainly in Northern China; the highest RR = 423.51, 95% CI: 240.96–722.32) for SARS. Fewer secondary clusters were identified after the “Wuhan lockdown”. The LISA cluster map detected a significantly high-low (Hubei) and low-high spatial clustering (Anhui, Hunan, and Jiangxi, in Central China) for COVID-19. Two significant high-high (Beijing and Tianjin) and low-high (Hebei) clusters were detected for SARS. Conclusions COVID-19 and SARS outbreaks exhibited distinct spatiotemporal clustering patterns at the provincial levels in mainland China, which may be attributable to changes in social and demographic factors, local government containment strategies or differences in transmission mechanisms.

Background: Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to the prognosis of cancer. We performed this study to explore the association between SNPs within microRNA binding sites and the prognosis of breast cancer.Methods: We carried out a two-stage study including 2647 breast cancer patients, with a median follow-up of 68 months (range 0-159). In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs significantly associated with breast cancer prognosis in another dataset using the TaqMan platform. Survival times was calculated, and Kaplan-Meier curves and Cox regression model were used to analyze survival of breast cancer patients with different genotypes.Results: We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (PConclusions: The LRKK2 rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population, and it could be used as a potential prognostic biomarker for breast cancer. Further studies are warranted.

Background To investigate the performance of primary ultrasound (P-US) screening for breast cancer, and that of supplemental ultrasound (S-US) screening for breast cancer after negative mammography (MAM). Methods Electronic databases (PubMed, Scopus, Web of Science, and Embase) were systematically searched to identify relevant studies published between January 2003 and May 2018. Only high-quality or fair-quality studies reporting any of the following performance values for P-US or S-US screening were included: sensitivity, specificity, cancer detected rate (CDR), recall rate (RR), biopsy rate (BR), proportion of invasive cancers among screening-detected cancers (ProIC), and proportion of node-negative cancers among screening-detected invasive cancers (ProNNIC). Results Twenty-three studies were included, including 12 studies in which S-US screening was used after negative MAM and 11 joint screening studies in which both primary MAM (P-MAM) and P-US were used. Meta-analyses revealed that S-US screening could detect 96% [95% confidential intervals (CIs): 82 to 99%] of occult breast cancers missed by MAM and identify 93% (95% CIs: 89 to 96%) of healthy women, with a CDR of 3.0/1000 (95% CIs: 1.8/1000 to 4.6/1000), RR of 8.8% (95% CIs: 5.0 to 13.4%), BR of 3.9% (95% CIs: 2.7 to 5.4%), ProIC of 73.9% (95% CIs: 49.0 to 93.7%), and ProNNIC of 70.9% (95% CIs: 46.0 to 91.6%). Compared with P-MAM screening, P-US screening led to the recall of significantly more women with positive screening results [1.5% (95% CIs:0.6 to 2.3%), P = 0.001] and detected significantly more invasive cancers [16.3% (95% CIs: 10.6 to 22.1%), P Conclusions Current evidence suggests that S-US screening could detect occult breast cancers missed by MAM. P-US screening has shown to be comparable to P-MAM screening in women with dense breasts in terms of sensitivity, specificity, cancer detection rate, and biopsy rate, but with higher recall rates and higher detection rates for invasive cancers.

Background: Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to the prognosis of cancer. We performed this study to explore the association between SNPs within microRNA binding sites and the prognosis of breast cancer.Methods: We carried out a two-stage study including 2647 breast cancer patients. In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs significantly associated with breast cancer prognosis in another dataset using the TaqMan platform. Survival times was calculated, and Kaplan-Meier curves and Cox regression model were used to analyze survival of breast cancer patients with different genotypes.Results: We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (PConclusions: The LRKK2 rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population, and it could be used as a potential prognostic biomarker for breast cancer. Further studies are warranted.

BackgroundBoth coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are caused by coronaviruses and have infected people in China and worldwide. We aimed to investigate whether COVID-19 and SARS exhibited similar spatial and temporal features at the provincial level in mainland China.MethodsThe number of people infected by COVID-19 and SARS were extracted from daily briefings on newly confirmed cases during the epidemics, as of Mar. 4, 2020 and Aug. 3, 2003, respectively. We depicted the spatiotemporal patterns of the COVID-19 and SARS epidemics using spatial statistics such as Moran’s I and the local indicators of spatial association (LISA).ResultsCompared to SARS, COVID-19 had a higher incidence. We identified 3 clusters (predominantly located in south-central China, highest RR=135.08) for COVID-19 and 4 clusters (mainly in Northern China, highest RR=423.51) for SARS. Fewer secondary clusters were identified after the “Wuhan lockdown”. The LISA cluster map detected a significantly high-low (Hubei) and low-high spatial clustering (Anhui, Hunan, and Jiangxi, in Central China) for COVID-19. Two significant high-high (Beijing and Tianjin) and low-high (Hebei) clusters were detected for SARS, although the global Moran’s I value was not significant.ConclusionsThe different spatiotemporal clustering patterns between COVID-19 and SARS could point to changes in social and demographic factors, local government containment strategies or differences in transmission mechanisms between these coronaviruses.

Background: ABO gene polymorphisms have been reported to be associated with the risk of multiple cancers and cardiocerebrovascular disease s. However, the results remained controversial. In this study, we conducted a systematic review and meta-analysis to clarify the association between two SNPs (rs505922 and rs657152) in ABO gene and cancers/ cardiocerebrovascular disease s. Method: All eligible case-control studies come from PubMed, Embase and Web of Science up to Jan. 1, 2019. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the corresponding associations. Sensitivity analysis, publication bias assessment, and heterogeneity test were performed using STATA 12.0. Results : A total of nineteen articles involving twenty-two case-control populations were included according to inclusion and exclusion criteria. Twelve populations (20,820 cases and 27,837 controls) were used to evaluate the relationship between rs505922 and overall cancers and nine populations (22,275 cases and 71,549 controls) were included to assess the association between rs505922 and cardiocerebrovascular diseases. The results showed a significant association between the rs505922 polymorphism and cancers (CvsT: OR=1.13, 95%CI=1.05-1.22, P =0.001), and cardiocerebrovascular diseases (OR=1.36, 95%CI=1.19-1.57, P