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.

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.

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 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.

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.

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.

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.

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.

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.

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.

Clinicopathological and surgical comparisons of differentiated thyroid cancer between China and the USA: A multicentered hospital-based study.

Background: Thyroid cancer (TC), was the fastest-rising tumor of all malignancies in the world and China, predominantly differentiated thyroid cancer (DTC). However, evidence on TC stage distribution and influencing factors of late-stage were limited in China. Methods: We carried out a retrospective study and enrolled TC patients who were first diagnosed and hospitalized in 8 hospitals in China in 2017. Logistic regression was used to evaluate associations between influencing factors and DTC stage. We extracted eligible primary DTC records newly diagnosed in 2017 from the USA's Surveillance, Epidemiology, and End Results (SEER) database. We compared clinicopathological features and surgical treatment between our DTC records and those from the SEER database. Results: A total of 1970 eligible patients were included, with 1861 DTC patients with known stage. Among patients ≥45 years old, males (OR = 1.76, 95%CI 1.17-2.65) and those with new rural cooperative medical scheme insurance (NCMS) (OR = 1.99, 95%CI 1.38-2.88) had higher risks of late-stage DTC (stage III-IV). Compared with SEER database, over-diagnosis is more common in China [more DTC patients with onset age< 45 years old (50.3 vs. 40.7%, P < 0.001), with early-stage (81.2 vs. 76.0%, P < 0.001), and with tumors<2cm (74.9 vs. 63.7%, P < 0.001)]. Compared with the USA, TC treatment is more conservative in China. The proportion of lobectomy in our database was significantly higher than that in the SEER database (41.3 vs. 17.0%, P < 0.001). Conclusions: Unique risk factors are found to be associated with late-stage DTC in China. The differences in the aspect of clinicopathological features and surgical approaches between China and the USA indicate that potential over-diagnosis and over-surgery exist, and disparities on surgery extent may need further consideration. The findings provided references for other countries with similar patterns.

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.

Artesunate Inhibits the Development of Esophageal Cancer by Targeting HK1 to Reduce Glycolysis Levels in Areas With Zinc Deficiency.

Esophageal cancer (EC) threatens many lives in China, especially in areas with high incidences of EC. Our previous studies proved that zinc deficiency (ZD) promotes the cell cycle, thus promoting the progression of EC in areas with a high incidence of EC. Artesunate could inhibit the cell cycle, thereby inhibiting the progression of EC. In this study, we first demonstrated the mechanism by which artesunate inhibits EC in vitro and then demonstrated that artesunate could reverse the ZD-promoted progression of EC before EC occurred in vivo. The results showed that artesunate could inhibit the cell cycle, metastasis, and glycolysis of EC cells. Artesunate could target HK1, promote HK1 degradation, and reduce the levels of HIF-1α and PKM2 expression, which are key glycolysis enzymes. The in vivo results showed that ZD could increase the expression of HK1 and increase the incidence of EC. Artesunate reduced the incidence of EC and decreased the level of HK1 expression before EC occurred. Artesunate has an anti-EC effect by inhibiting aerobic glycolysis and has the potential to be a drug that prevents EC in areas with a high risk of EC.

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.

Epidemiology and prognosis in young lung cancer patients aged under 45 years old in northern China.

To explore the epidemiological characteristics and prognosis of lung cancer in patients aged under 45 years old in northern China. The population-based database about lung cancer cases aged under 45y selected form the Hebei Provincial Cancer Registry Center from 2010-2015. Mortality data of young death from 1973 to 1975, 1990 to 1992, and 2004 to 2005 were extracted from the national retrospective survey of death. Mortality rates were calculated by the mortality database above in this analysis. Consecutive, 954 non-selected younger patients (< 45 years) and 2261 selected older patients (≥ 45 years) with pathologically diagnosed lung cancer treated at the Fourth Hospital of Hebei Medical University were included as the hospital-based database. Epidemiological, treatment outcomes and prognosis status from 2010 to 2017 were documented. A comparison with younger and older patients was also made. Multivariate analysis with young lung cancer patients was calculated by Cox regression model. The younger lung cancer mortality rate tended to slightly increase in Hebei Province, from 1.04 per100 000 in 1973 to 2.01 per 100 000 in 2015, but the PDR tended to decrease over the last 40 years. There were 954 younger and 2261 older lung cancer patients included in the hospital-based database. The proportions of patients who were female (50.84% vs 34.85%), family history of cancer (12.37% vs 6.32%), advanced stage at diagnosis (65.46% vs 60.77%) and adenocarcinoma (65.27% vs 61.11%) were relatively higher in the younger group than in the older group. The median OS were 23.0 months and 27.0 months between younger and older, the OS difference existed between the two groups (P = 0.001). In the younger patients, Cox regression showed that a family history of cancer, symptoms at diagnosis, pathology, stage at diagnosis and surgery were confirmed as independent factors affecting the prognosis. Mortality rates among younger lung cancer patients showed an increasing trend in northern China. The younger account for small but have unique characteristics, with higher proportions of female, family history of cancer, adenocarcinoma and advanced stages than the older group and had a trend of worse OS.

Participation and Yield of a Lung Cancer Screening Program in Hebei, China.

OBJECTIVE: Lung cancer screening has been widely conducted in Western countries. However, population-based lung cancer screening programs in Hebei in China are sparse. Our study aimed to assess the participation rate and detection rate of positive nodules and lung cancer in Hebei province. METHOD: In total, 228 891 eligible participants aged 40-74 years were enrolled in the Cancer Screening Program in Hebei from 2013 to 2019. A total of 54 846 participants were evaluated as the lung cancer high-risk population by a risk score system which basically followed the Harvard Risk Index and was adjusted for the characteristics of the Chinese population. Then this high-risk population was recommended for low-dose computed tomography (LDCT) screening. And all participants attended annual passive follow-up, and the active follow-up interval was based on radiologist's suggestion. All participants were followed-up until December 31, 2020. The overall, group-specific participation rates were calculated, and its associated factors were analyzed by a multivariable logistic regression model. Participation rates and detection of positive nodules and lung cancer were reported. RESULTS: The overall participation rate was 52.69%, where 28 899 participants undertook LDCT screening as recommended. The multivariable logistic regression model demonstrated that a high level of education, having disease history, and occupational exposure were found to be associated with the participation in LDCT screening. The median follow-up time was 3.56 person-years. Overall, the positive identification of lung nodules and suspected lung cancer were 12.73% and 1.46% through LDCT screening. After the native and passive follow-up, 257 lung cancer cases were diagnosed by lung cancer screening, and the detection rate of lung cancer was 0.89% in the screening group. And its incidence density was 298.72 per 100,000. Positive lung nodule rate and detection rate were increased with age. CONCLUSION: Our study identified personal and epidemiological factors that could affect the participation rate. Our findings could provide the guideline for precise prevention and control of lung cancer in the future.

Small cell lung cancer (SCLC) incidence and trends vary by gender, geography, age, and subcategory based on population and hospital cancer registries in Hebei, China (2008-2017).

BACKGROUND: Lung cancer is the leading cause of morbidity and mortality worldwide. Small cell lung cancer (SCLC) has been determined to be the most lethal lung malignancy. Few studies have previously analyzed the epidemiological characteristics of SCLC in China. This study analyzed the epidemiological characteristics of SCLC aiming to provide a reference for the prevention of SCLC in Hebei Province. METHODS: The epidemiological characteristics of SCLC using lung cancer data based on population and hospital cancer registries in Hebei Province between 2008 and 2017 were analyzed. RESULTS: The proportion of both population- and hospital-based SCLC cases displayed a significant increasing trend. Moreover, the proportion of males was higher than that for female based on population- and hospital-based cases. The proportion of hospital-based SCLC cases in counties was higher than that in cities, whereas there were no significant regional differences between cities and counties based on population. The proportion of both population- and hospital-based SCLC cases decreased consistently with increasing age. There was a difference between population- and hospital-based distribution of subcategories of SCLC. CONCLUSIONS: Significant increases in the proportion of both population- and hospital-based SCLC cases over recent years, particularly in males and in patients aged over 55 years, were observed. Research on the pathogenesis of SCLC in these patients and prevention is urgently required.

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.