Development and evaluation of a risk assessment tool for the personalized screening of breast cancer in Chinese populations: A prospective cohort study.

INTRODUCTION: Breast cancer is a significant contributor to female mortality, exerting a public health burden worldwide, especially in China, where risk-prediction models with good discriminating accuracy for breast cancer are still scarce. METHODS: A multicenter screening cohort study was conducted as part of the Cancer Screening Program in Urban China. Dwellers aged 40-74 years were recruited between 2014 and 2019 and prospectively followed up until June 30, 2021. The entire data set was divided by year of enrollment to develop a prediction model and validate it internally. Multivariate Cox regression was used to ascertain predictors and develop a risk-prediction model. Model performance at 1, 3, and 5 years was evaluated using the area under the curve, nomogram, and calibration curves and subsequently validated internally. The prediction model incorporates selected factors that are assigned appropriate weights to establish a risk-scoring algorithm. Guided by the risk score, participants were categorized into low-, medium-, and high-risk groups for breast cancer. The cutoff values were chosen using X-tile plots. Sensitivity analysis was conducted by categorizing breast cancer risk into the low- and high-risk groups. A decision curve analysis was used to assess the clinical utility of the model. RESULTS: Of the 70,520 women enrolled, 447 were diagnosed with breast cancer (median follow-up, 6.43 [interquartile range, 3.99-7.12] years). The final prediction model included age and education level (high, hazard ratio [HR], 2.01 [95% CI, 1.31-3.09]), menopausal age (≥50 years, 1.34 [1.03-1.75]), previous benign breast disease (1.42 [1.09-1.83]), and reproductive surgery (1.28 [0.97-1.69]). The 1-year area under the curve was 0.607 in the development set and 0.643 in the validation set. Moderate predictive discrimination and satisfactory calibration were observed for the validation set. The risk predictions demonstrated statistically significant differences between the low-, medium-, and high-risk groups (p < .001). Compared with the low-risk group, women in the high- and medium-risk groups posed a 2.17-fold and 1.62-fold elevated risk of breast cancer, respectively. Similar results were obtained in the sensitivity analyses. A web-based calculator was developed to estimate risk stratification for women. CONCLUSIONS: This study developed and internally validated a risk-adapted and user-friendly risk-prediction model by incorporating easily accessible variables and female factors. The personalized model demonstrated reliable calibration and moderate discriminative ability. Risk-stratified screening strategies contribute to precisely distinguishing high-risk individuals from asymptomatic individuals and prioritizing breast cancer screening. PLAIN LANGUAGE SUMMARY: Breast cancer remains a burden in China. To enhance breast cancer screening, we need to incorporate population stratification in screening. Accurate risk-prediction models for breast cancer remain scarce in China. We established and validated a risk-adapted and user-friendly risk-prediction model by incorporating routinely available variables along with female factors. Using this risk-stratified model helps accurately identify high-risk individuals, which is of significant importance when considering integrating individual risk assessments into mass screening programs for breast cancer. Current clinical breast cancer screening lacks a constructive clinical pathway and guiding recommendations. Our findings can better guide clinicians and health care providers.

Associations between experience of stressful life events and cancer prevalence in China: results from the China Kadoorie Biobank study.

BACKGROUND: Studies examining the relationships of stressful life events and cancer yielded inconsistent findings, while relevant evidence in mainland China is scarce. The current study sought to determine whether experience of stressful life events was associated with cancer prevalence in Chinese population. METHODS: We used cross-sectional data from the China Kadoorie Biobank study which that recruited 0.5 million Chinese adults aged 30 to 79 from 2004 to 2008. Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cancer associated with stressful life events reported at baseline. RESULTS: Among the 461,696 participants included in this analysis, 2,122 (0.46%) had self-reported cancer with the mean (SD) age was 57.12 (9.71) years. Compared to those without any stressful life event, participants who experienced 1 and 2 or more events had significantly higher odds of cancer, with the ORs of 1.80 (95% CI: 1.58-2.05) and 3.05 (2.18-4.28). For categories of work-, family-, and personal-related events, the OR of cancer was 1.48 (1.07-2.05), 2.06 (1.80-2.35), and 1.65 (1.17-2.33), respectively. Regarding the specific stressful life events, loss of income/living on debt, major conflict within family, death/major illness of other close family member, and major injury/traffic accident were significantly associated with increased odds of cancer, with the ORs of 2.64 (1.81-3.86), 1.73 (1.20-2.50), 2.36 (2.05-2.72), and 2.11 (1.43-3.13). CONCLUSION: Our findings suggested that experiences of cumulative and specific stressful life events were significantly associated with increased cancer prevalence in Chinese population.

High-throughput sequencing reveals Jatrorrhizine inhibits colorectal cancer growth by ferroptosis-related genes.

BACKGROUND: Colorectal cancer is a malignant tumor that poses a serious threat to human health. The main objective of this study is to investigate the mechanism by which Jatrorrhizine (JAT), a root extract from Stephania Epigaea Lo, exerts its anticancer effects in colorectal cancer. METHODS: We initially assessed the inhibitory properties of JAT on SW480 cells using MTT and cell scratch assays. Flow cytometry was employed to detect cell apoptosis. Differentially expressed genes were identified through high-throughput sequencing, and they were subjected to functional enrichment and signaling pathway analysis and PPI network construction. RT-qPCR was used to evaluate gene expression and identify critical differentially expressed genes. Finally, the function and role of differentially expressed genes produced by JAT-treated SW480 cells in colorectal cancer will be further analyzed using the TCGA database. RESULTS: Our study demonstrated that JAT exhibits inhibitory effects on SW480 cells at concentrations of 12.5µM, 25µM, 50µM, and 75µM without inducing cell apoptosis. Through high-throughput sequencing, we identified 244 differentially expressed genes. KEGG and GO analysis of high-throughput sequencing results showed that differentially expressed genes were significantly enriched in MAPK, Wnt, and P53 signaling pathways. Notably, JAT significantly altered the expression of genes associated with ferroptosis. Subsequent RT-qPCR showed that the expression of ferroptosis genes SLC2A3 and ASNS was significantly lower in JAT-treated SW480 cells than in the control group. Analysis by TCGA data also showed that ferroptosis genes SLC2A3 and ASNS were significantly highly expressed in COAD. The prognosis of SLC2A3 was significantly worse in COAD compared to the normal group. SLC2A3 may be a core target of JAT for the treatment of COAD. CONCLUSIONS: JAT can inhibit COAD growth by ferroptosis-related genes. And it is a potential natural substance for the treatment of COAD.

Association of high miR-27a, miR-206, and miR-214 expression with poor patient prognosis and increased chemoresistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, associated with early metastasis and recurrence as well as poor patient outcome. TNBC does not or weakly respond to hormonal or HER2-targeted therapies. Therefore, there is a strong need to identify other potential molecular targets for TNBC therapy. Micro-RNAs play important roles in the post-transcriptional regulation of gene expression. Thus, micro-RNAs, displaying an association between elevated expression and poor patient prognosis, may represent candidates for such novel tumor targets. In the present study, we evaluated the prognostic impact of miR-27a, miR-206, and miR-214 in TNBC via qPCR in tumor tissue (n=146). In univariate Cox regression analysis, elevated expression of all three analyzed micro-RNAs was significantly associated with shortened disease-free survival (hazard ratio [HR] for miR-27a: 1.85, P=0.038; miR-206: 1.83, P=0.041; miR-214: 2.06, P=0.012). In multivariable analysis, the micro-RNAs remained independent biomarkers for disease-free survival (HR for miR-27a: 1.99, P=0.033; miR-206: 2.14, P=0.018; miR-214: 2.01, P=0.026). Furthermore, our results suggest that elevated levels of these micro-RNAs are linked to enhanced resistance to chemotherapy. Based on the association of high expression levels with shortened patient survival and increased chemoresistance, miR-27a, miR-206, and miR-214 may represent novel molecular targets for TNBC.

A novel denoising method for low-dose CT images based on transformer and CNN.

Computed Tomography (CT) has become a mainstream imaging tool in medical diagnosis. However, the issue of increased cancer risk due to radiation exposure has raised public concern. Low-dose computed tomography (LDCT) technique is a CT scan with lower radiation dose than conventional scans. LDCT is used to make a diagnosis of lesions with the smallest dose of x-rays, and is currently mainly used for early lung cancer screening. However, LDCT has severe image noise, and these noises affect adversely the quality of medical images and thus the diagnosis of lesions. In this paper, we propose a novel LDCT image denoising method based on transformer combined with convolutional neural network (CNN). The encoder part of the network is based on CNN, which is mainly used to extract the image detail information. In the decoder part, we propose a dual-path transformer block (DPTB), which extracts the features of input of the skip connection and the features of input of the previous level through two paths respectively. DPTB can better restore the detail and structure information of the denoised image. In order to pay more attention to the key regions of the feature images extracted at the shallow level of the network, we also propose a multi-feature spatial attention block (MSAB) in the skip connection part. Experimental studies are conducted, and comparisons with the state-of-the-art networks are made, and the results demonstrate that the developed method can effectively remove the noise in CT images and improve the image quality in the evaluation metrics of peak signal to noise ratio (PSNR), structural similarity (SSIM), and root mean square error (RMSE) and is superior to the state-of-the-art models. Our method achieved 28.9720 of PSNR, 0.8595 of SSIM and 14.8657 of RMSE on the Mayo Clinic LDCT Grand Challenge dataset. For different noise level σ (15, 35, and 55) on the QIN_LUNG_CT dataset, our proposed also achieved better performances.

Disparity in Lung Cancer Screening Among Smokers and Nonsmokers in China: Prospective Cohort Study.

BACKGROUND: Low-dose computed tomography (LDCT) screening is effective in reducing lung cancer mortality in smokers; however, the evidence in nonsmokers is scarce. OBJECTIVE: This study aimed to evaluate the participant rate and effectiveness of one-off LDCT screening for lung cancer among smokers and nonsmokers. METHODS: A population-based prospective cohort study was performed to enroll participants aged between 40 and 74 years from 2013 to 2019 from 4 cities in Zhejiang Province, China. Participants who were evaluated as having a high risk of lung cancer from an established risk score model were recommended to undergo LDCT screening. Follow-up outcomes were retrieved on June 30, 2020. The uptake rate of LDCT screening for evaluated high-risk participants and the detection rate of early-stage lung cancer (stage 0-I) were calculated. The lung cancer incidence, lung cancer mortality, and all-cause mortality were compared between the screened and nonscreened groups. RESULTS: At baseline, 62.56% (18,818/30,079) of smokers and 6% (5483/91,455) of nonsmokers were identified as high risk (P<.001), of whom 41.9% (7885/18,818) and 66.31% (3636/5483) underwent LDCT screening (P<.001), respectively. After a median follow-up of 5.1 years, 1100 lung cancer cases and 456 all-cause death cases (116 lung cancer death cases) were traced. The proportion of early-stage lung cancer among smokers was 60.3% (173/287), which was lower than the proportion of 80.3% (476/593) among nonsmokers (P<.001). Among smokers, a higher proportion was found in the screened group (72/106, 67.9%) than the nonscreened group (56/114, 49.1%; P=.005), whereas no significance was found (42/44, 96% vs 10/12, 83%; P=.20) among nonsmokers. Compared with participants who were not screened, LDCT screening in smokers significantly increased lung cancer incidence (hazard ratio [HR] 1.39, 95% CI 1.09-1.76; P=.007) but reduced lung cancer mortality (HR 0.52, 95% CI 0.28-0.96; P=.04) and all-cause mortality (HR 0.47, 95% CI 0.32-0.69; P<.001). Among nonsmokers, no significant results were found for lung cancer incidence (P=.06), all-cause mortality (P=.89), and lung cancer mortality (P=.17). CONCLUSIONS: LDCT screening effectively reduces lung cancer and all-cause mortality among high-risk smokers. Further efforts to define high-risk populations and explore adequate lung cancer screening modalities for nonsmokers are needed.

A Pair of Prognostic Biomarkers in Triple-Negative Breast Cancer: KLK10 and KLK11 mRNA Expression.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor patient prognosis and limited therapeutic options. A lack of prognostic biomarkers and therapeutic targets fuels the need for new approaches to tackle this severe disease. Extracellular matrix degradation, release, and modulation of the activity of growth factors/cytokines/chemokines, and the initiation of signaling pathways by extracellular proteolytic networks, have been identified as major processes in the carcinogenesis of breast cancer. Members of the kallikrein-related peptidase (KLK) family contribute to these tumor-relevant processes, and are associated with breast cancer progression and metastasis. In this study, the clinical relevance of mRNA expression of two members of this family, KLK10 and KLK11, has been evaluated in TNBC. For this, their expression levels were quantified in tumor tissue of a large, well-characterized patient cohort (n = 123) via qPCR. Although, in general, the overall expression of both factors are lower in tumor tissue of breast cancer patients (encompassing all subtypes) compared to normal tissue of healthy donors, in the TNBC subtype, expression is even increased. In our cohort, a significant, positive correlation between the expression levels of both KLKs was detected, indicating a coordinate expression mode of these proteases. Elevated KLK10 and KLK11 mRNA levels were associated with poor patient prognosis. Moreover, both factors were found to be independent of other established clinical factors such as age, lymph node status, or residual tumor mass, as determined by multivariable Cox regression analysis. Thus, both proteases, KLK10 and KLK11, may represent unfavorable prognostic factors for TNBC patients and, furthermore, appear as promising potential targets for therapy in TNBC.

CCR5 as a prognostic biomarker correlated with immune infiltrates in head and neck squamous cell carcinoma by bioinformatic study.

BACKGROUND: C-C chemokine receptor 5 (CCR5) has recently been recognized as an underlying therapeutic target for various malignancies. However, the association of CCR5 with prognosis in the head and neck squamous cell carcinoma (HNSC) patients and tumor-infiltrating lymphocytes (TILs) is unclear. METHODS: In the current experiment, methods such as the Tumor Immune Estimation Resource Analysis (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier plotter Analysis were used to comprehensively evaluate the expression of CCR5 in human various malignancies and the clinical prognosis in HNSC patients. Subsequently, we used the TIMER database and the TISIDB platform to investigate the correlation between CCR5 expression levels and immune cell infiltration in the HNSC tumor microenvironment. Furthermore, immunomodulatory and chemokine profiling were performed using the TISIDB platform to analyse the correlation between CCR5 expression levels and immunomodulation in HNSC patients. RESULTS: We found that CCR5 expression in HNSC tumor tissues was significantly upregulated than in normal tissues. In HNSC, patients with high CCR5 expression levels had worse overall survival (OS, HR = 0.59, p = 0.00015) and worse recurrence-free survival (RFS, HR = 3.27, p = 0.00098). Upregulation of CCR5 expression is closely associated with immunomodulators, chemokines, and infiltrating levels of CD4+ T cells, neutrophils, macrophages, and myeloid dendritic cells. Furthermore, upregulated CCR5 was significantly associated with different immune markers in the immune cell subsets of HNSC. CONCLUSIONS: High expression of CCR5 plays an important prognostic role in HNSC patients and may serve as a prognostic biomarker correlated with immune infiltration, and further studies are still needed to investigate therapeutic targeting HNSC patients in the future.

Protective role of hydrogen sulfide against diabetic cardiomyopathy via alleviating necroptosis.

Diabetic cardiomyopathy lacks effective and novel methods. Hydrogen sulfide (H2S) as the third gasotransmitter plays an important role in the cardiovascular system. Our study was to elucidate the protective effect and possible mechanism of H2S on diabetic cardiomyopathy from the perspective of necroptosis. Leptin receptor deficiency (db/db) mice and streptozotocin (STZ)-induced diabetic cystathionine-γ-lyase (CSE) knockout (KO) mice were investigated. In addition, cardiomyocytes were stimulated with high glucose. We found that plasma H2S level, myocardial H2S production and CSE mRNA expression was impaired in the diabetic mice. CSE deficiency exacerbated diabetic cardiomyopathy, and promoted myocardial oxidative stress, necroptosis and inflammasome in STZ-induced mice. CSE inhibitor dl-propargylglycine (PAG) aggravated cell damage and oxidative stress, deteriorated necroptosis and inflammasome in cardiomyocytes with high glucose stimulation. H2S donor sodium hydrosulfide (NaHS) improved diabetic cardiomyopathy, attenuated myocardial oxidative stress, necroptosis and the NLR family pyrin domain-containing protein 3 (NLRP3) in db/db mice. NaHS also alleviated cell damage, oxidative stress, necroptosis and inflammasome in cardiomyocytes with high glucose stimulation. In Conclusion, H2S deficiency aggravated mitochondrial damage, increased reactive oxygen species accumulation, promoted necroptosis, activated NLRP3 inflammasome, and finally exacerbated diabetic cardiomyopathy. Exogenous H2S supplementation alleviated necroptosis to suppress NLRP3 inflammasome activation and attenuate diabetic cardiomyopathy via mitochondrial dysfunction improvement and oxidative stress inhibition. Our study provides the first evidence and a new mechanism that necroptosis inhibition by a pharmacological manner of H2S administration protected against diabetic cardiomyopathy. It is beneficial to provide a novel strategy for the prevention and treatment of diabetic cardiomyopathy.

Innovation in sweet rice wine with high antioxidant activity: Eucommia ulmoides leaf sweet rice wine.

The dried leaves of Eucommia ulmoides Oliv., which have a high nutritional value, are mainly used in both medicine and food. In this study, we used Eucommia ulmoides leaf superfine powder as an additive in the fermentation of glutinous rice (Semen Oryzae Glutinosae) to develop a new healthcare product, Eucommia leaf sweet rice wine. The fermentation conditions were optimized, and the nutrient value was evaluated through analyses of metabolites, functional compositions, antioxidant capacity, and antihyperglycemic, antihyperlipidemic, and antihypertensive abilities. The metabolic analysis demonstrated that Eucommia leaf sweet rice wine contained a large number of flavonoids and other metabolites. Eucommia leaf sweet rice wine had higher contents of flavonoid (729.0 ± 0.11 µg/g), free amino acids (55.0 ± 0.37 µg/g), polyphenol (150.0 ± 0.43 µg/g), and polysaccharide (0.25 ± 0.03 µg/g) than traditional sweet rice wine, with increases of 14.7, 2.6, 6.8, and 6.3 times, respectively. In addition, an analysis of antioxidant capacity in vitro revealed that Eucommia leaf sweet rice wine had a high level of activity in scavenging 2, 2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, and hydroxyl radicals, as well as in reducing iron, indicating that it was a strong antioxidant. Furthermore, Eucommia leaf sweet rice wine had a high cholate binding capacity and could significantly inhibit α-amylase, α-glucosidase, and angiotensin-converting enzyme (ACE) activity. In conclusion, this study developed a new application of Eucommia leaf in sweet rice wine fermentation and brewed Eucommia leaf sweet rice wine with strong antioxidant activity and positive antihypertensive, antihyperglycemic, and antihyperlipidemic effects in vitro. This study suggests new opportunities for the wider use of Eucommia ulmoides leaves and adds variety to sweet rice wine.

Cancer incidence and mortality in Zhejiang Province, Southeast China, 2016: a population-based study.

BACKGROUNDS: Cancer is one of the main causes of death worldwide, seriously threatening human health and life expectancy. We aimed to analyze the cancer incidence and mortality rates during 2016 in Zhejiang Province, Southeast China. METHODS: Data were collected from 14 population-based cancer registries across Zhejiang Province of China. Cancer incidence and mortality rates stratified by sex and region were analyzed. The crude rate, age-standardized rate, age-specific and region-specific rate, and cumulative rate were calculated. The proportions of 10 common cancers in different groups and the incidence and mortality rates of the top five cancers in different age groups were also calculated. The Chinese national census of 2000 and the world Segi population was used for calculating the age-standardized incidence and mortality rates. RESULTS: The 14 cancer registries covered a population of 14,250,844 individuals, accounting for 29.13% of the population of Zhejiang Province. The total reported cancer cases and deaths were 55,835 and 27,013, respectively. The proportion of morphological verification (MV%) was 78.95% of the population, and percentage of incident cases identified through death certificates only (DCO%) was 1.23% with a mortality-to-incidence ratio (M/I ratio) of 0.48. The crude incidence rate in Zhejiang cancer registration areas was 391.80/105; the age-standardized incidence rate of the Chinese standard population (ASIRC) and the age-standardized incidence rate of the world standard population (ASIRW) were 229.76/105 and 220.96/105, respectively. The incidence rate in men was higher than that in women. The incidence rate increased rapidly after 45 years of age and peaked in individuals aged 80 to 84 years. The top 10 incidence rates of cancers were lung cancer, female breast cancer, thyroid cancer, colorectal cancer, stomach cancer, liver cancer, prostate cancer, cervical cancer, esophageal cancer, and pancreatic cancer (from highest to lowest). The crude mortality rate in Zhejiang cancer registration areas was 189.55/105; the age-standardized mortality rate of the Chinese standard population (ASMRC) and the age-standardized mortality rate of the world standard population (ASMRW) were 94.46/105 and 93.42/105, respectively. The mortality rate in men was higher than that in women, and the male population in rural areas was higher than that in urban areas. The cancer mortality rate increased rapidly after 50 years of age and peaked in individuals aged 85+ years. The top 10 mortality rates of cancers were lung cancer, liver cancer, stomach cancer, colorectal cancer, pancreatic cancer, esophageal cancer, female breast cancer, prostate cancer, lymphoma, and leukemia (from highest to lowest). CONCLUSIONS: Lung cancer, female breast cancer, thyroid cancer, colorectal cancer, prostate cancer, liver cancer, and stomach cancer were the most common cancers in Zhejiang Province. Effective prevention and control measures should be established after considering the different characteristics of cancers in urban and rural areas.

Protective role of sirtuin3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation.

Sirtuin3 (SIRT3) is involved in reactive oxygen species (ROS), cell metabolism, apoptosis and inflammation. However, the exact role of SIRT3 in macrophages during pathophysiological process of atherosclerosis remains unclear. The present study was to investigate the possible effects and mechanisms of SIRT3 on lipid uptake and foam cells transforming in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages. Compared with wild-type (WT) mice, SIRT3 deficiency further increased foam cell formation and cellular cholesterol accumulation, exacerbated oxidative stress, impaired mitochondrial permeability potential, decreased optic atrophy 1 (OPA1) but enhanced dynamin-related protein 1 (DRP1) expression, and promoted NLR family pyrin domain-containing protein 3 (NLRP3) activation in ox-LDL-stimulated macrophages from SIRT3 knockout (KO) mice. Dihydromyricetin (DMY), a potential compound to enhance SIRT3 expression, significantly inhibited cellular cholesterol accumulation, suppressed foam cell formation, improved mitochondrial function, attenuated oxidative stress, and alleviated NLRP3 activation in ox-LDL-stimulated macrophages. Moreover, above protective effects of DMY was unavailable in macrophages from SIRT3 KO mice. Collectively, the study demonstrated the protective role of SIRT3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation, which is beneficial to provide novel strategy for atherosclerosis prevention and treatment.

Elevated levels of both microRNA 378 (miR-378) and kallikrein-related peptidase 4 (KLK4) mRNA are associated with an unfavorable prognosis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) patients have the worst outcome among all breast cancer subtypes. In oral squamous carcinoma cells, miR-378 was reported to target the mRNA of kallikrein-related peptidase 4 (KLK4), resulting in inhibition of cell proliferation, migration and invasion, induction of apoptosis, and reduction of tumor growth in vivo. Similarly, a miR-378/KLK4 axis has been proposed in prostate cancer. Here, we analyzed the correlation between miR-378 and KLK4 mRNA expression and determined the prognostic impact of both factors in TNBC. miR-378 and KLK4 mRNA expression levels were determined by quantitative PCR in tumor tissue of TNBC patients (n=103) and correlated with clinical parameters and patients' survival. There was no significant correlation between miR-378 and KLK4 mRNA expression. In univariate Cox regression analysis, elevated miR-378 expression was significantly associated with shortened disease-free survival (DFS, P=0.047) and overall survival (OS, P=0.031), high KLK4 mRNA levels were linked to a worse DFS (P=0.033). Combination of KLK4 mRNA and miR-378 (KLK4+miR-378, low/low versus high and/or high) allowed even better discrimination between favorable and unfavorable prognosis (DFS, P=0.008; OS, P=0.025). In multivariable analysis, miR-378 and KLK4+miR-378 expression remained independent predictive factors for DFS (P=0.014, P=0.010, respectively) and OS (P=0.016, P=0.049, respectively), while KLK4 mRNA only showed a trend towards significance for DFS (P=0.061). Our findings suggest that in TNBC there is no significant impact of miR-378 on KLK4 expression. Both factors, miR-378 and, to a lesser extent, KLK4 mRNA represent unfavorable prognostic markers in TNBC patients.

The association between diabetes and thyroid cancer risk: a hospital-based case-control study in China.

BACKGROUND: Previous studies have indicated inconsistent relationships of diabetes with thyroid cancer risk, yet little is known in China. In this study, we aimed to investigate the associations between diabetes, diabetes duration and the risk of thyroid cancer in Chinese population. METHODS: A 1:1 matched case-control study was performed between 2015 and 2017 in Zhejiang Province including 2,937 thyroid cancer cases and 2,937 healthy controls. Odds ratios (ORs) with 95 % confidence intervals (CIs) for thyroid cancer were estimated in logistic regression models. Specific effects stratified by age, as well as sex, body mass index (BMI) and family history of diabetes were also examined. RESULTS: Overall, neither diabetes (OR = 0.75, 95 % CI: 0.21-2.73) nor diabetes duration (OR = 0.14, 95 % CI: 0.02-1.22 for diabetes duration ≦ 5 years; OR = 2.10, 95 % CI: 0.32-13.94 for diabetes duration > 5 years) was significantly associated with thyroid cancer. In stratified analyses, significant lower risk of thyroid cancer was observed among subjects with diabetes and shorter diabetes duration ( ≦ 5 years), but limited to those who were aged more than 40 years, female, overweight/obese and had positive family history of diabetes. CONCLUSIONS: Diabetes and shorter diabetes duration were significantly associated with decreased risk of thyroid cancer in individuals characterized by older age, female sex, higher BMI and positive family history of diabetes.

Sleep duration and behavioral correlates in middle and high school students: a cross-sectional study in Zhejiang province, China.

OBJECTIVE: To investigate the sleep duration and correlates from lifestyle, dietary and weight control behaviors in Chinese adolescents. METHODS: Data were from 2017 Zhejiang Youth Risk Behavior Survey. A total of 17059 adolescents were included in this study and sleep duration and other behaviors information was collected via a self-reported questionnaire. Regression coefficients (ß), calculated by multivariable linear regression, were used to assess the effects of related behaviors on sleep duration, adjusting for potential confounding factors. RESULTS: Overall, the mean sleep duration in adolescents was 7.99 h. Ever smoking, engaging in moderate physical activity and muscle strengthening activity, attending physical education classes, and watching television were significantly associated with longer sleep duration (P trend ≦0.01 for all). Adolescents with breakfast, fruits, vegetables, milk and soft drinks intake were more likely to have longer sleep duration (P trend <0.05 for all). Weight perception of overweight and weight control behaviors including exercising and eating less food, fewer calories were significantly associated with the short sleep duration (P trend <0.05 for all). CONCLUSION: Chinese adolescents slept less than the counterparts in Western countries. Various lifestyle, dietary and weight control behaviors were associated with sleep duration.

Menstrual, reproductive and hormonal factors and thyroid cancer: a hospital-based case-control study in China.

BACKGROUND: There have been considerable studies on the effects of reproductive factors on thyroid cancer risk, while findings are inconsistent. In this analysis, we aimed to investigate the associations between menstrual, reproductive and hormonal factors with thyroid cancer occurrence in a population of Chinese women. METHODS: Using data from a 1:1 matched case-control study performed between 2015 and 2017 in Zhejiang Province of China, a second analysis of 2261 pairs of female subjects was conducted. The possible effects for thyroid cancer were evaluated in logistic regression models by odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Later age at first pregnancy (for > 25 vs. ≦ 20 years, OR: 0.47, 95% CI 0.23-0.96) and longer duration of breast feeding (for 6-12 vs. ≦ 6 months, OR: 0.49, 95% CI 0.24-0.98) were significantly associated with decreased occurrence of thyroid cancer, while no trend was observed. Stratified by age at enrollment, only the association with duration of breast feeding remained significant, but limited to younger women (≦ 50 years). CONCLUSIONS: Our results suggested that women with later age at first pregnancy or longer breast feeding duration were less likely to have thyroid cancer. These findings supported an influence role of reproductive factors in thyroid cancer risk.

FAM65A as a novel prognostic biomarker in human tumors reveal by a pan-cancer analysis.

BACKGROUND: Family with sequence similarity 65 member A (FAM65A), also known as RIPOR1, is differentially expressed between human tumor and non-tumor tissues in kinds of cancers. In addition, it was reported that the product of FAM65A may be a biomarker for cholangiocarcinoma patients. However, there is still no evidence on the relationship between the FAM65A and different types of tumors. Our study is mainly for exploring the prognostic values of FAM65A in pan-cancer and for further discovering a potential therapeutics target. METHODS: We analyzed FAM65A expression, prognostic values, genetic alteration, protein phosphorylation, immune infiltration and enrichment analysis across different types of human malignant tumors based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Additionally, Real-Time PCR (RT-qPCR) was performed to further confirm the roles of FAM65A in the pathogenesis of colorectal cancer. RESULTS: We found that FAM65A expression was associated with the prognosis of multiple human tumors, especially colorectal cancer. Moreover, we also observed that FAM65A was highly expressed in colorectal cancer through RT-qPCR. We observed that decreasing phosphorylation level of the S351 locus in colon adenocarcinoma, uterine corpus endometrial carcinoma and lung adenocarcinoma. And the expression of FAM65A was positively related to cancer-associated fibroblasts (CAFs) infiltration in many tumors, such as colon adenocarcinoma. Therefore, FAM65A may be a potential prognostic biomarker of human tumors.

Prognostic value of kallikrein-related peptidase 7 (KLK7) mRNA expression in advanced high-grade serous ovarian cancer.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian cancer. A growing body of evidence suggests tumor-supporting roles of several members of the kallikrein-related peptidase (KLK) family, including KLK5 and KLK7, in this cancer subtype. In normal physiology, KLK5 and KLK7 are the major proteases involved in skin desquamation. Moreover, in several cancer types KLK5 and KLK7 co-expression has been observed. Recently, we have shown that elevated KLK5 mRNA levels are associated with an unfavorable prognosis in HGSOC. Therefore, the aim of this study was to investigate the clinical significance of KLK7 mRNA expression and to explore its relation to KLK5 levels in HGSOC. METHODS: mRNA expression levels of KLK7 were quantified by qPCR in a well-characterized patient cohort afflicted with advanced high-grade serous ovarian cancer (FIGO III/IV, n = 139). Previously determined KLK5 mRNA as well as KLK5 and KLK7 antigen concentrations were used to evaluate the relationship between the expression patterns of both factors on the mRNA as well as protein level in tumor tissue of HGSOC patients. RESULTS: There were strong, significant positive correlations between KLK5 and KLK7 both at the mRNA and the protein level, suggesting coordinate expression of these proteases in HGSOC. In univariate analyses, elevated KLK7 levels as well as the combination of KLK5 + KLK7 (high and/or high versus low/low) were significantly associated with worse progression-free survival (PFS). High mRNA expression levels of KLK7 and the combination of KLK5 and KLK7 showed a trend towards significance for overall survival (OS). In multivariate analyses, KLK7 mRNA expression represented an unfavorable, statistically significant independent predictor for PFS and OS. CONCLUSIONS: The findings imply that both increased KLK5 and KLK7 mRNA expression levels represent unfavorable prognostic biomarkers in advanced high-grade serous ovarian cancer, whereby multivariate analyses indicate that KLK7 mRNA exhibits a stronger predictive value as compared to KLK5 mRNA and the combination of KLK5 and KLK7.

Body-mass index and long-term risk of sepsis-related mortality: a population-based cohort study of 0.5 million Chinese adults.

BACKGROUND: Sepsis represents a major worldwide healthcare burden. However, how body-mass index (BMI) is related to the long-term risk of sepsis-related mortality in low- and middle-income countries remains uncertain. METHODS: We examined the associations of sepsis-related mortality with both baseline BMI and waist circumference (WC) using data from China Kadoorie Biobank, a prospective cohort recruited during 2004-2008 and followed up to December 2016. After excluding participants with chronic obstructive pulmonary disease, tuberculosis, cancer, heart disease, and stroke, and omitting the first 3 years of follow-up, 440,763 participants remained for analysis. RESULTS: During a median follow-up of 10.0 years, 1957 sepsis-related deaths (3,134,870 person-years) were included for analysis. Compared with reference BMI of 22.5 to < 25.0 kg/m2, the multivariable-adjusted hazard ratios (HRs) for sepsis-related mortality were 2.42 (95% CIs 2.07-2.84) for BMI of < 18.5, 1.59 (1.36-1.85) for 18.5 to < 20.0, 1.21 (1.06-1.38) for 20.0 to < 22.5, 0.97 (0.83-1.13) for 25.0 to < 27.5, 0.98 (0.80-1.21) for 27.5 to < 30.0, and 1.22 (0.93-1.60) for ≥ 30.0 kg/m2. Further adjustment for WC led to slightly augmentation of the effect size for the lower BMI groups and null association in the obese group. In the association analysis between WC and sepsis-related mortality, compared with the middle quintile group, only the highest quintile group showed an increased risk of sepsis-related mortality after adjusted for BMI (HR = 1.54; 95% CI 1.28-1.84). CONCLUSIONS: Underweight, lower normal weight, and abdominal obesity are associated with increased future risk of sepsis-related mortality over 10 years in the Chinese population. The double burden of underweight and obesity indicates a heavy sepsis burden faced by low- and middle-income countries.

Synthetic chloroinconazide compound exhibits highly efficient antiviral activity against tobacco mosaic virus.

BACKGROUND: Development of anti-plant-virus compounds and improvement of biosafety remain hot research topics in controlling plant viral disease. Tobacco mosaic virus (TMV) infects all tobacco species as well as many other plants worldwide and causes severe losses in tobacco production. To date, no efficient chemical treatments are known to protect plants from virus infection. Therefore, the search for a highly active antiviral compound with high efficacy in field application is required. RESULTS: We reported the synthesis of a novel antiviral halogenated acyl compound Chloroinconazide (CHI) using tryptophan as a substrate and examined its anti-TMV activity. We found that CHI displayed the ability to strongly inhibit the infection of TMV on Nicotiana benthamiana via multiple mechanisms. We observed that CHI was able to impair the virulence of TMV by directly altering the morphological structure of virions and increasing the activity of anti-oxidative enzymes, resulting in reduced TMV-induced ROS production during infection of the plant. In addition, the expression of salicylic acid-responsive genes was significantly increased after CHI application. However, after application of CHI on SA-deficient NahG plants no obvious anti-TMV activity was observed, suggesting that the SA signaling pathway was required for CHI-induced anti-TMV activity associated with reduced infection of TMV. CHI exhibited no effects on plant growth and development. CONCLUSION: The easily synthesized CHI can actively induce plant resistance against TMV as well as act on virus particles and exhibits high biosafety, which provides a potential for commercial application of CHI in controlling plant virus disease in the future. © 2020 Society of Chemical Industry.