Analysis of the incidence and mortality trends of esophageal cancer in cancer registry areas of China and Japan.

This study aims to analyze the prevalence trend of esophageal cancer in Japan and China to provide suggestions for the prevention and treatment of esophageal cancer. The results showed that the incidence rate for the years 2010-2018 significantly decreased with an APC of 5.66%, and the mortality rate from 2010 to 2015 had an APC of -5.87% in China. However, the incidence rate of Japanese women showed an upward trend, with an APC of 4.09% from 2010 to 2019. The mortality rate of esophageal cancer in Japan showed a downward trend, with an APC of -2.96% from 2010 to 2021. From 2010 to 2018, Chinese esophageal squamous cell carcinoma accounted for the highest proportion, accounting for 85.96%, with the largest distribution in the middle, accounting for 47.25%. Patients are mostly diagnosed at stage III, and the relative survival rate from 2012 to 2015 was 30.3%. Japan also has the highest proportion of squamous cell carcinoma, and the lesions are also mostly located in the middle segment. While Japanese esophageal cancer patients are mostly diagnosed at stage I, and the relative survival rate was 41.5% in Japan from 2009 to 2011. The results of this article indicate that the current prevalence of esophageal cancer in China and Japan is generally declining, and the quality of life of patients is gradually improving, but effective screening and prevention strategies are still needed to reduce the burden of this disease.

Lung cancer risk and exposure to air pollution: a multicenter North China case-control study involving 14604 subjects.

BACKGROUND: For North Chinese lung cancer patients, there is limited study on the distribution of air pollution and smoking related features based on analyses of large-scale, high-quality population datasets. The aim of the study was to fully analyze risk factors for 14604 Subjects. METHODS: Participants and controls were recruited in 11 cities of North China. Participants' basic information (sex, age, marital status, occupation, height, and weight), blood type, smoking history, alcohol consumption, history of lung-related diseases and family history of cancer were collected. PM2.5 concentration data for each year in each city of the study area from 2005 to 2018 were extracted based on geocoding of each person's residential address at the time of diagnosis. Demographic variables and risk factors were compared between cases and matched controls using a univariate conditional logistic regression model. Multivariate conditional logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for risk factors in univariate analysis. The nomogram model and the calibration curve were developed to predict lung cancer probability for the probability of lung cancer. RESULTS: There was a total of 14604 subjects, comprising 7124 lung cancer cases and 7480 healthy controls included in the study. Marital status of unmarried persons, people with a history of lung-related disease, corporate personnel and production /service personnel were protective factors for lung cancer. People younger than 50 years old, people who were smoking and quit smoking, people who had been drinking consistently, people with family history of cancer and PM2.5 exposure were proven to be a risk factor for lung cancer. The risk of lung cancer varied with sex, smoking status and air pollution. Consistent alcohol consumption, persistent smoking and smoking quit were risk factors for lung cancer in men. By smoking status, male was risk factor for lung cancer in never smokers. Consistent alcohol consumption added risk for lung cancer in never smokers. The combined effects of PM2.5 pollution exposure and ever smoking aggravated the incidence of lung cancer. According to air pollution, lung cancer risk factors are completely different in lightly and heavily polluted areas. In lightly polluted areas, a history of lung-related disease was a risk factor for lung cancer. In heavily polluted areas, male, consistent alcohol consumption, a family history of cancer, ever smokers and smoking quit were all risk factors for lung cancer. A nomogram was plotted and the results showed that PM2.5 was the main factor affecting the occurrence of lung cancer. CONCLUSIONS: The large-scale accurate analysis of multiple risk factors in different air quality environments and various populations, provide clear directions and guidance for lung cancer prevention and precise treatment.

MicroRNA-29b regulates the radiosensitivity of esophageal squamous cell carcinoma by regulating the BTG2-mediated cell cycle.

BACKGROUND: Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable due to old age or advanced stage; thus, radio- and chemotherapy are considered the standard treatments for these patients. However, due to the radiation resistance of tumor cells that may arise during radiotherapy, results are still not satisfactory. The authors' previous studies found that microRNA can affect radiosensitivity, and further microRNA research was conducted to improve the radiosensitivity of ESCC. METHODS: Cells were treated with silent miR-29b (si-miR-29b). Thereafter,proliferation, colony formation, cell cycle, and apoptosis were determined. The luciferase reporting assay was used to confirm the direct interaction between miR-29b and BTG2. Serum samples and clinical follow-up data of 75 elderly or advanced ESCC patients who could not tolerate surgery were collected. RESULTS: The expression level of miR-29 in ESCC serum was closely correlated to radiosensitivity (χ2 =8.36, p < 0.05) and correlated with overall survival (OS; hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.24-0.90). Function assays demonstrated that the number of cell clones increased after radiometry radiation, and the cell cycle was blocked in the G0/G1 phase (from 37.2 to 56.9%) in the si-miR-29b transfection group. Expression of BTG2 was upregulated and expression of cyclin D1 was downregulated (p < 0.05). Transfection of si-BTG2 can reverse this result and restore the expression level of cyclin D1 (p < 0.05). The target gene BTG2 of miR-29b was predicted using a bioinformatics tool and confirmed by dual-luciferase reporter assay. CONCLUSION: Silencing of miR-29b in ESCC cells can increase expression of BTG2 and decrease the level of intracellular cyclin D1, resulting in cell cycle arrest and accumulation in the G0/G1 phase. Because G0/G1-phase cells are insensitive to radiotherapy, the sensitivity of radiotherapy is reduced.

Incidence and mortality of laryngeal cancer in China, 2015.

OBJECTIVE: Using data from cancer registries to estimate laryngeal cancer incidence and mortality in China, 2015. METHODS: Data submitted from 501 cancer registries were checked and evaluated according to the criteria of data quality control and 368 registries' data were qualified for the final analysis. Data were stratified by area (urban/rural), sex, age group and combined with national population data to estimate laryngeal cancer incidence and mortality in China, 2015. China population census in 2000 and Segi's population were used for age-standardized. RESULTS: The percentage of cases morphological verified (MV%) of laryngeal cancer was 74.18%. The percentage of death certificate-only cases (DCO%) was 2.10%. And the mortality to incidence (M/I) ratio was 0.55. About 25,300 new cases of laryngeal cancer were diagnosed in 2015 and 13,700 deaths were reported. The crude rate of laryngeal cancer was 1.84 per 100,000 (males and females were 3.20 and 0.42 per 100,000, respectively). Age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 1.18 and 1.19 per 100,000, respectively. The cumulative incidence rate (0-74 years old) was 0.15%. The crude mortality rate was 1.00 per 100,000. Age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 0.61 and 0.61 per 100,000, respectively, with the cumulative rate (0-74 years old) was 0.07%. Incidence and mortality of laryngeal cancer in males were higher than those in females. And the rates in urban areas were higher than those in rural areas. CONCLUSIONS: The incidence and mortality of laryngeal cancer in China were low. And the rates were significantly higher in males than in females. Risk factor control and targeted prevention should be strengthened.

Incidence and mortality of esophagus cancer in China, 2008-2012.

OBJECTIVE: To analyze the incidence and mortality rates of esophagus cancer in China from 2008 to 2012. METHODS: Incident and mortality cases of esophagus cancer were retrieved from the National Central Cancer Registry (NCCR) database collecting from 135 cancer registries in China during 2008-2012. The incidence and mortality rates of esophagus cancer were calculated by area (urban/rural), region (eastern, middle, western), gender and age group (0, 1-4, 5-84 by 5 years and 85+ years). China census in 2000 and Segi's world population were applied for age-standardized rates. Joinpoint model was used for time-trend analysis. RESULTS: The crude incidence rate of esophagus cancer was 22.57/100,000. The age-standardized incidence rates by China standard population (ASIRC) and by world standard population (ASIRW) were 14.58/100,000 and 14.80/100,000, respectively. The crude mortality rate of esophagus cancer was 17.19/100,000. The age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 10.80/100,000 and 10.86/100,000 respectively. Incidence and mortality rates of esophagus cancer were higher in males than in females and higher in rural areas than in urban areas. The crude incidence rate in middle areas was the highest among all areas, followed by western areas and eastern areas. The age-specific incidence rate of esophagus cancer was relatively low in age groups before 40 years old and then increased after 45 years old. It peaked in the age group of 80-84 years. The patterns of age-specific mortality rates of esophagus cancer were close to those of age-specific incidence rates. The ASIRC of esophagus cancer decreased dramatically by 29.87% between 2003 and 2012, from 14.33/100,000 to 10.05/100,000. The esophagus cancer incidence rate decreased by 3.76% per year (P>0.05). The mortality rate of esophagus cancer decreased annually over the decades from 2003 to 2012 in China (P>0.05). In females, the annual percentage change (APC) of mortality rate was -5.43% [95% confidence intervals (95% CI): -6.50%, -4.30%] (P<0.05) and the mortality rate of esophagus cancer in rural females was statistically significant (APC: -3.20%, 95% CI: -4.20%, -2.20%) (P<0.05). CONCLUSIONS: The focus of prevention and treatment for esophagus cancer is strengthening primary prevention of esophageal cancer, and promoting esophagus cancer secondary prevention to reduce incidence and mortality rates of esophagus cancer, prolong survival rate of patients and decline the burden of esophagus cancer in China.

Estimated cancer incidence and mortality in Hebei province, 2012.

OBJECTIVE: This study estimates the numbers of new cancer cases and cancer deaths in Hebei province using incidence and mortality data from 9 population-based cancer registries in 2012. METHODS: The data of new diagnosed cancer cases and cancer deaths in 2012 were collected from 9 population-based cancer registries of Hebei province in 2015. All the data met the National Central Cancer Registry of China (NCCR) criteria of data quality. The pooled data analysis was stratified by areas (urban/rural), gender, age group (0, 1.4, 5.9, 10.14, …, 85+) and cancer type. New cancer cases and deaths in Hebei province were estimated using age-specific rates and corresponding provincial population in 2012. The 10 most common cancers in different groups and the cumulative rates were calculated. Chinese population census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. RESULTS: All cancer registries covered 4,986,847 populations, 6.84% of Hebei provincial population (2,098,547 in urban and 2,888,300 in rural areas). The percentage of cases morphologically verified (MV%) and death certificate-only cases (DCO%) were 76.40% and 4.72%, respectively. The mortality to incidence rate ratio (M/I) was 0.64. In 2012, it is estimated that there were about 187,900 new diagnosed cancer cases and 119,800 cancer deaths in Hebei province. The incidence rate of cancer was 258.12/100,000 (275.75/100,000 in males, 239.78/100,000 in females), and the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 210.65/100,000 and 208.50/100,000, with the cumulative incidence rates (0.74 years old) of 24.46%. The cancer incidence and ASIRC were 256.99/100,000 and 211.32/100,000 in urban areas and 258.94/100,000 and 209.99/100,000 in rural areas, respectively. The cancer mortality rate was 164.63/100,000 (201.85/100,000 in males, 125.92/100,000 in females). Agestandardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 137.30/100,000 and 137.39/100,000 with the cumulative mortality rate (0.74 years old) of 14.58%, respectively. The cancer mortality rate in rural areas (167.16/100,000) was higher than that in urban areas (161.16/100,000). The most common cancers were lung cancer, stomach cancer, breast cancer, esophageal cancer, liver cancer and colorectal cancer, which accounted for 72.31% of all cancer cases. Lung cancer, stomach cancer, liver cancer, esophageal cancer and colorectal cancer were the major causes of cancer death in Hebei province, which accounted for 75.24% of all cancer deaths. The cancer spectrum differs between urban and rural, males and females in both incidence and mortality rates. CONCLUSIONS: The most common cancers were lung cancer, stomach cancer, esophageal cancer, breast cancer, liver cancer and colorectal cancer in Hebei province.

Pancreatic cancer incidence and mortality patterns in China, 2011.

OBJECTIVE: The National Central Cancer Registry (NCCR) collected population-based cancer registration data in 2011 from all cancer registries in China. The incidence and mortality rates for pancreatic cancer were compiled and pancreatic cancer incident new cases and deaths were estimated. METHODS: A total of 234 cancer registries submitted cancer data to NCCR. Data from 177 cancer registries were qualified and compiled for cancer statistics in 2011. Pancreatic cancer cases were extracted and analyzed from the national database. The pooled data were stratified by area (urban/rural), gender and age group (0, 1-4, 5-9, 10-14…85+). Pancreatic cancer incident cases and deaths were estimated using age-specific rates and national population in 2010. The national census in 2000 and Segi's population were used for age-standardized rates. RESULTS: All 177 cancer registries (77 in urban and 100 in rural areas) covered 175,310,169 populations (98,341,507 in urban and 76,968,662 in rural areas). The morphology verified pancreatic cancer cases (MV%) accounting for 40.52% and 4.33% of pancreatic cancer incident cases were identified through death certifications only (DCO%) with mortality to incidence ratio (M/I) of 0.91. The estimated number of newly diagnosed pancreatic cancer cases and deaths were 80,344 and 72,723 in 2011, respectively. The crude incidence rate was 5.96/100,000 (males 6.57/100,000, females 5.32/100,000). The age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 4.27/100,000 and 4.23/100,000 respectively, ranking 10(th) among all cancers. Pancreatic cancer incidence rate and ASIRC were 7.03/100,000 and 4.94/100,000 in urban areas whereas they were 4.84/100,000 and 3.56/100,000 in rural areas. The incidence rate of pancreatic cancer of 33 cancer registries increased from 3.24/100,000 in 2003 to 3.59/100,000 in 2011 with an annual percentage change (APC) of 1.44. The pancreatic cancer mortality rate was 5.40/100,000 (males 5.88/100,000, females 4.89/100,000), ranking 6(th) among all cancers. The age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 3.81/100 000 and 3.79/100 000. The pancreatic cancer mortality and ASMRC were 6.47/100,000 and 4.48/100,000 in urban areas, and 4.27/100,000 and 3.08/100,000 in rural areas, respectively. The mortality rates of pancreatic cancer showed an approximately 1.14-fold increase, from 2.85/100,000 in 2003 to 3.26/100,000 in 2011, with an APC of 1.68. CONCLUSIONS: The burden of pancreatic cancer is increasing in China. Identification of high-risk population and adequate treatment and prevention are important.

Generation and characterization of a novel human IgG1 antibody against vascular endothelial growth factor receptor 2.

VEGF and its receptors, especially VEGFR2 (KDR), are known to play a critical role in angiogenesis under both physiological and pathological conditions, including cancer and angiogenic retinopathies. This study was aimed at developing a fully human IgG1 antibody (mAb-04) constructed from a phage-derived scFv, targeting the VEGF/VEGFR2 pathway. Firstly, an innovative transfection system, containing two recombinant expression vectors (pMH3 and pCApuro), were introduced into CHO-s cells and clones with higher yield selected accordingly. After an optimal fermentation condition was determined, fed-batch fermentation was performed in 5-L bioreactor with a final yield up to 60 mg/L. Further, cell proliferation, wound healing, transwell invasion, tube formation and chick embryo chorioallantoic membrane assays showed significant anti-angiogenic activity of mAb-04 in vitro and in vivo. In addition, the results of Western blotting indicated the ability of mAb-04 to inhibit VEGF-induced VEGFR2 signaling pathway. Finally, ADCC assay demonstrated that mAb-04 is capable of mediating tumor cell killing in presence of effector cells. This study has therefore proved that the full-length antibody targeting human VEGFR2 has potential clinical applications in the treatment of cancer and other diseases where pathological angiogenesis is involved.

Association of radiotherapy for stage I-III breast cancer survivors and second primary malignant cancers: a population-based study.

PURPOSE: With life span extending, breast cancer survivors may face the possibility of developing second primary cancers (SPCs). The objective of this research is to investigate the risk factors, risk attribute to radiotherapy and the survivalship for SPCs. METHODS: A total of 445 523 breast cancer patients were enrolled from Surveillance, Epidemiology, and End Results database in 2000-2018. The risk factors for SPCs development were confirmed by competing risk model, and then were integrated to the nomogram establishment. The cumulative incidence of SPCs including SBC (second breast cancer), SGC (second gynecological cancer), and SLC (second lung cancer) were estimated. The radiotherapy-associated risk for SPCs were evaluated by Poisson regression in radiotherapy and no-radiotherapy. Propensity score matching was used to reduce possible bias for survival comparison. RESULTS: There were 57.63% patients in radiotherapy. The risk factors for developing SPCs were age, year, race, tumor size, stage, radiotherapy, grade, surgery, and histology. The cumulative incidence of SPCs was 7.75% in no-radiotherapy and 10.33% in radiotherapy. SLC, SBC, and SGC also appeared the similar results. The increased risk of developing SPCs were associated with radiotherapy in majority subgroups. The dynamic radiotherapy-associated risk for SPCs by age slightly increased risk was observed. Regardless radiotherapy or no-radiotherapy, the 10-year overall survival for SBC (radiotherapy: 59.41%; no-radiotherapy: 55.53%) and SGC (radiotherapy: 48.61%; no-radiotherapy: 35.53%) were worse than that among matched patients with only primary cancers. CONCLUSIONS: Breast cancer survivors remained a high radiotherapy-associated risk for developing SPCs. The prognosis in radiotherapy was better than in no-radiotherapy for some specific SPCs. Largely attention should be paid to these patients.

Periplasmic expression optimization of VEGFR2 D3 adopting response surface methodology: antiangiogenic activity study.

Vascular endothelial growth factor (VEGF) is one of the most significant mediators of angiogenesis, which interacts with a specific membrane receptor: VEGF receptor 2 (VEGFR2). Studies elsewhere have shown that, a VEGF-blocker can regulate several vital processes of tumor promotion. However, there is no literature evidence of investigation on antiangiogenic ability of single domain 3 of VEGFR-2 (VEGFR2 D3), as the key domain in signal transduction of VEGF. In this article, we aimed at developing an efficient method for producing soluble form of this receptor as therapeutic applications. The optimization of the production of soluble VEGFR2 D3 in Escherichia coli was firstly done by testing the periplasmic expression in different expression systems using three osmotic shock methods. To enhance the yield, vital factors were selected from nine factors by Plackett-Burman design and the level of each viral factor was optimized via a response surface methodology based central composite design. After purification and identification of the protein, the bioactivity assays: quantitative ELISA, VEGF-induced proliferation and in vivo chick chorioallantoic membrane assay were employed in our study. The outcome showed that, E. coli Rosetta-gami (DE3)/pET22b-VEGFR2 D3 was the most effective expression system. Furthermore, the inducing time, peptone and glycerol concentration affected the periplasmic expression of VEGFR2 D3 significantly. The corresponding level was also optimized. The bioactivity assay studies showed VEGFR2 D3 could suppress both VEGF stimulated cell proliferation in vitro and neovascularization in vivo. We have therefore provided a novel antiangiogenic drug candidate relating to VEGF-VEGFR2 pathway.

Stratifin (SFN) Regulates Cervical Cancer Cell Proliferation, Apoptosis, and Cytoskeletal Remodeling and Metastasis Progression Through LIMK2/Cofilin Signaling.

The aberrant expression of Stratifin (SFN) is intricately associated with the initiation and progression of numerous tumors. This study aims to investigate whether SFN regulates the metastasis of cervical cancer cells through the LIMK2/Cofilin signaling pathway. In this study, we compared the expression of SFN in normal cervical tissues and cervical carcinoma tissues. We established SFN overexpression and SFN silencing cellular models to assess the invasive and migratory capabilities of cervical cancer cells using transwell and scratch assays. YO-PRO-1/PI and EdU staining were employed to evaluate apoptotic and proliferative capacities, while Actin-Tracker Green-488 was utilized to investigate cytoskeletal remodeling. The expression levels of SFN, LIMK2, p-LIMK2, Cofilin, and p-Cofilin were examined through Western blotting and immunofluorescence. Our findings revealed elevated expression of SFN in cervical squamous cell carcinoma tissues. SFN overexpression was observed to enhance invasion and migration of cervical cancer cells, induce cytoskeletal remodeling, facilitate cell proliferation, and suppress apoptosis. Furthermore, SFN overexpression upregulated the expression levels of LIMK2, p-LIMK2, Cofilin, and p-Cofilin. Conversely, silencing SFN exerted opposite effects. SFN plays an important role in the diagnosis of cervical cancer. SFN can regulate cervical cancer cell proliferation, apoptosis, cytoskeletal remodeling and metastasis through LIMK2/Cofilin signaling.

Cost-effectiveness evaluation of risk-based breast cancer screening in Urban Hebei Province.

To evaluate the implementations of Cancer Screening Program in Urban Hebei and to model the cost-effectiveness of a risk-based breast Cancer Screening Program. Women aged 40-74 years were invited to participate the Cancer Screening Program in Urban Hebei form 2016 to 2020 by completing questionnaires to collect information about breast cancer exposure. Clinical screening including ultrasound and mammography examination were performed. We developed a Markov model to estimate the lifetime costs and benefits, in terms of quality-adjusted life years (QALY), of a high-risk breast Cancer Screening Program. Nine screening strategies and no screening were included in the study. The age-specific incidence, transition probability data and lifetime treatment costs were derived and adopted from other researches. Average cost-effectiveness ratios (ACERs) were estimated as the ratios of the additional costs of the screening strategies to the QLYG compared to no screening. Incremental cost-effectiveness ratios (ICERs) were calculated based on the comparison of a lower cost strategies to the next more expensive and effective strategies after excluding dominated strategies and extendedly dominated strategies. ICERs were used to compare with a willingness-to-pay (WTP) threshold. Sensitivity analysis was explored the influence factors. A total of 84,029 women completed a risk assessment questionnaire, from which 20,655 high-risk breast cancer females were evaluated, with a high-risk rate of 24.58%. There were 13,392 high-risk females completed the screening program, with participation rate was 64.84%. Undergoing ultrasound, mammography and combined screening, the suspicious positive detection rates were 15.00%, 9.20% and 19.30%, and the positive detection rates were 2.11%, 2.76% and 3.83%, respectively. According to the results by Markov model, at the end of 45 cycle, the early diagnosis rates were 55.53%, 60.68% and 62.47% underwent the annual screening by ultrasound, mammography and combined, the proportion of advanced cancer were 17.20%, 15.85% and 15.36%, respectively. Different screening method and interval yield varied. In the exploration of various scenarios, annual ultrasound screening is the most cost-effective strategy with the ICER of ¥116,176.15/QALY. Sensitivity analyses demonstrated that the results are robust. Although it was not cost effective, combined ultrasound and mammography screening was an effective strategy for higher positive detection rate of breast cancer. High-risk population-based breast cancer screening by ultrasound annually was the most cost-effective strategy in Urban Hebei Province.

Effect of high-level PM2.5 on survival in lung cancer: a multicenter cohort study from Hebei Province, China.

Globally, air pollution is the fourth leading risk factor for death, while lung cancer (LC) is the leading cause of cancer-related death. The aim of this study was to explore the prognostic factors of LC and the influence of high fine particulate matter (PM2.5) on LC survival. Data on LC patients were collected from 133 hospitals across 11 cities in Hebei Province from 2010 to 2015, and survival status was followed up until 2019. The personal PM2.5 exposure concentration (µg/m3) was matched according to the patient's registered address, calculated from a 5-year average for every patient, and stratified into quartiles. The Kaplan-Meier method was used to estimate overall survival (OS), and Cox's proportional hazard regression model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The 1-, 3-, and 5-year OS rates of the 6429 patients were 62.9%, 33.2%, and 15.2%, respectively. Advanced age (75 years or older: HR = 2.34, 95% CI: 1.25-4.38), subsite at overlapping (HR = 4.35, 95% CI: 1.70-11.1), poor/undifferentiated differentiation (HR = 1.71, 95% CI: 1.13-2.58), and advanced stages (stage III: HR = 2.53, 95% CI: 1.60-4.00; stage IV: HR = 4.00, 95% CI: 2.63-6.09) were risk factors for survival, while receiving surgical treatment was a protective factor (HR = 0.60, 95% CI: 0.44-0.83). Patients exposed to light pollution had the lowest risk of death with a 26-month median survival time. The risk of death in LC patients was greatest at PM2.5 concentrations of 98.7-108.9 µg/m3, especially for patients at advanced stage (HR = 1.43, 95% CI: 1.29-1.60). Our study indicates that the survival of LC is severely affected by relatively high levels of PM2.5 pollution, especially in those with advanced-stage cancer.

Establishment and validation of a prognostic model for gastric cancer patients of Hebei Province in China.

BACKGROUND: Hebei Province is a high-risk area for gastric cancer in China, and there is currently no survival prediction model for gastric cancer patients in Hebei Province. This study aimed to build the best survival prediction model for gastric cancer patients in Hebei Province. METHODS: The development dataset included 1,993 hospitalized gastric cancer patients from the Hebei Cancer Registration Project during 2016 and 2017. Three tree-based machine learning methods [survival trees (ST), random survival forests (RSF), and gradient boosting machines (GBM)] and Cox, were used to develop the models by ten-fold cross validation with 200 iterations. California Chinese hospitalized gastric cancer patients were used as external test models. In addition, we compared the multivariable group with the Tumor Node Metastasis (TNM) group. RESULTS: The 3- and 5-year cancer-specific survival (CSS) rates of the development dataset were 57.07% and 44.48%, respectively. For predicting the 3-year CSS rates of gastric cancer patients of multivariable group, the C-indexes in train datasets were 0.75, 0.72, 0.79 and 0.76 for Cox, ST, RSF and GBM. Multivariable group performed better than TNM group. The predictive ability of Cox and RSF were superior to ST and GBM. A nomogram was established to predict the 3- and 5-year CSS rates of gastric cancer patients. CONCLUSIONS: The nomogram was useful for facilitating clinicians to predict the survival of gastric cancer patients, and identifying high-risk patients so as to adopt more reasonable treatment plans.

Machine learning for predicting the survival in osteosarcoma patients: Analysis based on American and Hebei Province cohort.

Osteosarcoma, a rare malignant tumor, has a poor prognosis. This study aimed to find the best prognostic model for osteosarcoma. There were 2912 patients included from the SEER database and 225 patients from Hebei Province. Patients from the SEER database (2008-2015) were included in the development dataset. Patients from the SEER database (2004-2007) and Hebei Province cohort were included in the external test datasets. The Cox model and three tree-based machine learning algorithms (survival tree [ST], random survival forest [RSF] and gradient boosting machine [GBM]) were used to develop the prognostic models by 10-fold cross-validation with 200 iterations. Additionally, performance of models in the multivariable group was compared with the TNM group. The 3-year and 5-year cancer specific survival (CSS) were 72.71% and 65.92% in the development dataset, respectively. The predictive ability in the multivariable group was superior to that in the TNM group. The calibration curves and consistency in the multivariable group were superior to those in the TNM group. The Cox and RSF models performed better than the ST and GBM models. A nomogram was constructed to predict the 3-year and 5-year CSS of osteosarcoma patients. The RSF model can be used as a nonparametric alternative to the Cox model. The constructed nomogram based on the Cox model can provide reference for clinicians to formulate specific therapeutic decisions both in America and China.

Evaluation of a population-based breast cancer screening in North China.

BACKGROUND: Despite mammography-based screening for breast cancer has been conducted in many countries, there are still little data on participation and diagnostic yield in population-based breast cancer screening in China. METHODS: We enrolled 151,973 eligible women from four cities in Hebei Province within the period 2013-2021 and followed up until December 31, 2021. Participants aged 40-74 who assessed as high risk were invited to undergo breast ultrasound and mammography examination. Overall and group-specific participation rates were calculated. Multivariable analyses were used to estimate the factors associated with participation rates. The diagnostic yield of both screening and no screening groups was calculated. We further analyzed the stage distribution and molecular subtype of breast cancer cases by different modes of cancer detection. RESULTS: A total of 42,547 participants were evaluated to be high risk of breast cancer. Among them, 23,009 subjects undertook screening services, with participation rate of 54.08%. Multivariable logistic regression model showed that aged 45-64, high education level, postmenopausal, current smoking, alcohol consumption, family history of breast cancer, and benign breast disease were associated with increased participation of screening. After median follow-up of 3.79 years, there were 456 breast cancer diagnoses of which 65 were screen-detected breast cancers (SBCs), 27 were interval breast cancers (IBCs), 68 were no screening cancers, and 296 were cancers detected outside the screening program. Among them, 92 participants in the screening group (0.40%) and 364 in the non-screening group (0.28%) had breast cancer detected, which resulted in an odds ratio of 1.42 (95% CI 1.13-1.78; P = 0.003). We observed a higher detection rate of breast cancer in the screening group, with ORs of 2.42 (95% CI 1.72-3.41) for early stage (stages 0-I) and 2.12 (95% CI 1.26-3.54) for luminal A subtype. SBCs had higher proportion of early stage (71.93%) and luminal A subtype (47.22%) than other groups. CONCLUSIONS: The significant differences in breast cancer diagnosis between the screening and non-screening group imply an urgent need for increased breast cancer awareness and early detection in China.

Effect of intra-operative chemotherapy with 5-fluorouracil and leucovorin on the survival of patients with colorectal cancer after radical surgery: a retrospective cohort study.

BACKGROUND: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. METHODS: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. RESULTS: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). CONCLUSIONS: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. TRIAL REGISTRATION: chictr.org.cn, ChiCTR 2100043775.

Disparities in stage at diagnosis among breast cancer molecular subtypes in China.

BACKGROUND: Disease stage at diagnosis and molecular subtypes are the main determinants of breast cancer treatment strategies and prognosis. We aimed at examining the disparities and factors associated with the stage at diagnosis among the molecular subtypes in breast cancer patients in China. METHODS: We identified patients with first primary breast cancer diagnosed between January 1, 2016, and December 31, 2017, from 23 hospitals in 12 provinces in China. We analyzed the proportion of non-early-stage (stages II-IV) breast cancer cases based on the family history of breast cancer, body mass index (BMI), insurance status, and molecular subtypes. Multivariable analyses were used to estimate the factors associated with non-early-stage diagnosis among the molecular subtypes. We further compared these estimates with that in the United States using the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 9398 Chinese were identified with first primary invasive breast cancer. Of the 8767 patients with known stages, the human epidermal growth factor receptor 2 (HER2)-enriched subtype had the highest proportion of stages II-IV (76.6%) patients, followed by triple-negative breast cancer (73.2%), luminal B (69.9%), and luminal A (62.3%). The percentage of non-early-stage patients was higher in women with overweight or obesity than in those with a body mass index (BMI) <25 kg/m2 (adjusted odds ratio [OR] 1.3, 95% confidence interval (CI) 1.1-1.4). Patients with a family history of breast cancer had a higher likelihood of early-stage (adjusted OR 0.7, 0.5-0.8) breast cancer. Patients with rural insurance had a substantially higher risk of non-early-stage disease than those with urban insurance (adjusted OR 1.8, 1.4-2.2). Regarding the subtype, being overweight/obese only increased the risk of non-early-stage in luminal A breast cancer. Compared with the United States, China had a higher proportion of non-early-stage breast cancer for all subtypes, with the largest gap in luminal A (adjusted OR 2.2, 95% CI 2.0-2.4). CONCLUSION: The wide disparities in stage at breast cancer diagnosis imply that China urgently needs to improve early breast cancer diagnosis and health equity.

Baicalein Inhibits the Progression and Promotes Radiosensitivity of Esophageal Squamous Cell Carcinoma by Targeting HIF-1A.

Purpose: To explore the mechanism of the effect of baicalein on radioresistance of esophageal cancer, and to provide ideas for the treatment of patients with poor radiotherapy effect of esophageal cancer. Methods: The glycolytic rate assay kit was used to detect the changes in glycolytic metabolism in esophageal cancer cells after treatment with baicalein, and mass spectrometry was used to detect whether baicalein could affect the level of glycolysis-related metabolites in esophageal cancer cells. The binding of baicalein to the target protein was simulated by molecular docking technique, the protein expression level was detected by Western Blot, and the changes in the cell cycle were detected by flow cytometry. Results: Radiation combined with baicalein could significantly inhibit the proliferation and migration of esophageal cancer cells compared with that of 6 Gy rays alone. The results of the glycolytic rate assay showed that baicalein could inhibit the glycolysis of esophageal cancer cells. Metabonomic studies showed that baicalein could affect the expression levels of glycolysis-related metabolites. The results of network pharmacology showed that baicalein could target several key glycolysis enzymes and glycolysis-related proteins, such as HIF-1A. The results of the WB experiment showed that glycolysis-related proteins and cycle-related proteins were down-regulated after baicalein treatment. Conclusion: The main mechanism of baicalein inhibiting radiation resistance of esophageal cancer cells is that targeting HIF-1A protein regulates glucose metabolism and then regulates Cyclin D1/CDK4 axis to change the cell cycle.

Epidemiological characteristics and risk factors of lung adenocarcinoma: A retrospective observational study from North China.

Background: The main aim of the study was to determine the risk factors of lung adenocarcinoma and to analyze the variations in the incidence of lung adenocarcinoma according to time, sex, and smoking status in North China. Methods: Patients with lung cancer in local household registries diagnosed and treated for the first time in the investigating hospital were enrolled from 11 cities in North China between 2010 and 2017. Baseline characteristics and tumor-related information were extracted from the patients' hospital medical record, clinical course records, and clinical examination. Some of the variables, such as smoking, alcohol consumption, medical history, and family history of cancer, were obtained from interviews with the enrolled patients. The statistical method used were the chi-square test and multi-factor logistic regression analysis. The time trend was statistically analyzed using Joinpoint regression models, and p values were calculated. Results: A total of 23,674 lung cancer cases were enrolled. People in severely polluted cities were at higher risk for lung adenocarcinoma (p < 0.001). Most patients with lung adenocarcinoma had no history of lung-related diseases (p = 0.001). Anatomically, lung adenocarcinoma was more likely to occur in the right lung (p < 0.001). Non-manual labor workers were more likely to develop from lung adenocarcinoma than manual workers (p = 0.015). Notably, non-smokers were more likely to develop lung adenocarcinoma than smokers (p < 0.001). The proportion of lung adenocarcinoma increased significantly in Hebei Province (p < 0.001). Among non-smokers, the proportion of lung adenocarcinoma showed a higher rise than in smokers (p < 0.001). Conclusions: Lung adenocarcinoma is the most common histological type of lung cancer in North China (Hebei Province), and the proportion of lung adenocarcinoma is increasing, especially among non-smokers. Lung adenocarcinoma is more common in women, severely polluted cities, individuals with no history of lung-related diseases, in the right lung, and in non-smokers. These can serve as a great guide in determining the accuracy of lung adenocarcinoma high-risk groups and lung cancer risk assessment models.