Objective:To explore the incidence and mortality of digestive system cancers, and the trend of the disease burden attributed to different risk factors in population in China.Methods:Data were obtained from the GLOBOCAN 2020 and the Global Burden of Disease Study in 2019 databases and only the data from the Chinese population were included. Using Excel 2019 and R 4.2.1 software, indicators including age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life year (DALY) rate and its rate of change were used to illustrate the disease burden of digestive system cancers attributed to different factors and their trends.Results:In 2020, the ASIR of digestive system cancers in China was 83.00/100 000, and the ASMR was 63.80/100 000. The numbers of digestive system cancer cases and deaths increased with age, and more cases and deaths occurred in men than in women in all age groups. The age-standardized DALY rate of esophageal cancer, gastric cancer and liver cancers showed decreasing trends in China from 1990 to 2019 (rate of change: -45.26%, -46.87%, and -65.63%, respectively), whereas the age-standardized DALY rate of pancreatic cancer, colorectal cancer and gallbladder and biliary tract cancer showed increasing trends (rate of change: 67.61%, 30.52%, and 7.21%, respectively). The trend of the mortality rate was consistent with the DALY rate. Compared with the age-standardized DALY rate attributed to behavioral factors, the annual proportion of the age-standardized DALY rate attributed to metabolic factors to the total age-standardized DALY rate of esophageal cancer, liver cancer, pancreatic cancer, and colorectal cancer increased from 1990 to 2019. There was no significant change in the rank of age-standardized DALY rate of gastric cancer, liver cancer, pancreatic cancer, and gallbladder and biliary tract cancer attributed to different risk factors in China from 1990 to 2019, but the rank of certain attributed risk factors for the age-standardized DALY rate of esophageal cancer and colorectal cancer moved ahead (esophageal cancer: high BMI; colorectal cancer: low milk intake, and low whole-grain intake).Conclusions:The incidence and mortality of digestive system cancers was serious in China in 2020, and the annual proportion of the disease burden of digestive system cancers attributed to metabolic factors increased from 1990 to 2019. The rank of attributed risk factors for several digestive system cancers changed significantly.

Objective:To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China.Methods:Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values.Results:A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening.Conclusion:To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

Objective:To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States.Methods:A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF).Results:In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection.Conclusions:China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

Objective:To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China.Methods:Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values.Results:A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening.Conclusion:To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

Objective:To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States.Methods:A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF).Results:In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection.Conclusions:China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

Background::Thyroid cancer (TC) is the most common malignancy of the endocrine system. This study aimed to assess the global distribution of TC incidence and mortality in 2022, as well as to predict the burden for the year 2050.Methods::Data from the GLOBOCAN 2022 database were used to analyze the age-standardized incidence and mortality rates of TC by sex, age group (<55 years and ≥55 years), country, world region, and level of Human Development Index (HDI) for 185 countries. The predicted incidence and mortality burden for 2050 was calculated based on demographic projections.Results::In 2022, an estimated 821,214 new TC cases and 47,507 TC-related deaths occurred worldwide. The age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were higher in women (ASIR: 13.60 per 100,000; ASMR: 0.53 per 100,000) than in men (ASIR: 4.60 per 100,000; ASMR: 0.35 per 100,000). The ASIR in high HDI countries was approximately ten times higher than that in low HDI countries for both sexes, with relatively similar ASMR across regions. Among 185 countries, China had the largest number of TC cases (accounting for 56.77% of total cases) and TC-related deaths (accounting for 24.35% of global TC-related deaths), with the highest ASIR in men (13.30 per 100,000). Worldwide, approximately 64.63% of TC cases occurred in populations under 55 years old, while nearly 82.99% of TC-related deaths occurred in populations aged 55 years and above. If the rates stay the same as in 2022, it is projected that approximately 1,100,000 new TC cases and 91,000 TC-related deaths will occur in 2050, indicating a 34.15% and 89.58% increase, respectively.Conclusions::TC is a highly frequent cancer worldwide with disparities across regions, genders, and age groups. Our results provide light on the worldwide TC disease burden and facilitate regionally customized prevention measures.

Objective:To investigate the role of NG2 cells in generating and maintaining neuropathic pain in rats after spinal cord injury (SCI).Methods:According to random number table method, 100 healthy adult male SD rats were divided into control group ( n=20, without any intervention), sham-operated group ( n=40, exposed T 10 segment without spinal cord impact) and SCI group ( n=40, exposed T 10 segment and constructed SCI model by improved Allen's method). One d before, and 14, 21 and 28 d after surgery, Von Frey fiber probe was used to detect the rat hindlimb mechanical withdrawal threshold (MWT); immunofluorescent staining was used to detect the proportion of NG2-positive cells in spinal dorsal horn cells; Western blotting was used to detect chondroitin sulfate proteoglycan (CSPG) expression in spinal dorsal horn of rats. Results:Fourteen, 21 and 28 d after surgery, SCI group had significantly lower hindlimb MWT, and significantly higher proportion of NG2-positive cells in spinal dorsal horn cells and CSPG expression in spinal dorsal horn than control group and sham-operated group ( P<0.05). One d before, and 14, 21 and 28 d after surgery, in SCI group, hindlimb MWT decreased firstly and increased secondly, proportion of NG2-positive cells in spinal dorsal horn cells increased firstly and decreased secondly, and CSPG expression in spinal dorsal horn increased firstly and decreased secondly. Except for those 21 and 28 d after surgery, hindlimb MWT, proportion of NG2-positive cells in spinal dorsal horn cells, and CSPG expression in spinal dorsal horn showed significant differences between each two time points ( P<0.05). In SCI group, hindlimb MWT was negatively correlated with proportion of NG2-positive cells in spinal dorsal horn cells ( r=-0.876, P<0.001), and CSPG expression was positively correlated with proportion of NG2-positive cells in spinal dorsal horn cells ( r=0.927, P<0.001). Conclusion:NG2 cell proliferation and increased CSPG expression secreted by NG2 cells in spinal cord tissues after SCI generate and maintain neuropathic pain.

Objective:To investigate the potential pleiotropism of cancer-related single nucleotide polymorphisms (SNPs) among Chinese population.Methods:Based on the catalogue of GWAS jointly constructed by the National Human Genome Research Institute and the European Institute of Bioinformatics, according to population origin (Chinese population and non-Chinese population) and disease traits (cancer and non-cancer traits). All SNPs found by GWAS before August 2020 were divided into four categories: cancer in Chinese population, non-cancer in Chinese population, cancer in non-Chinese population and non-cancer in non-Chinese population. The number, correlation and linkage of the four categories of SNPs were described.Results:By August 2020, a total of 196 813 SNPs from 4 096 GWAS were included in the GWAS directory. The information that SNPs refer to unknown or were not related to the disease was excluded, and 117 441 independent SNPs were finally included. There were 619 SNPs related to cancer and 9 569 SNPs related to non-cancer disease in Chinese population, respectively. There were 4 624 SNPs related to cancer and 106 448 SNPs related to non-cancer disease (trait) in non-Chinese population, respectively. Three SNPs, rs2736100, rs6983267 and rs401681, were associated with two or more types of cancer in both Chinese and non-Chinese populations. Seven SNPs, rs7705526, rs2736100, rs10993994, rs2735839, rs4430796, rs174537 and rs9271588, were associated with cancer and non-cancer diseases in both Chinese and non-Chinese populations, respectively.Conclusion:There is a potential pleiotropism of cancer-related SNPs in Chinese population.

The traditional proportional hazard model is commonly used to investigate the association between main outcome and predictor variables. However, the endpoints in medical studies are often not unique. The analyses of labeling other competing outcomes other than the main outcome as censored data will theoretically lead to a biased estimate of the risk of main outcome. Although the traditional competitive risk model can adjust the influence of other outcomes on the risk of the main outcome, it can not directly compare the differences on the risks of different outcomes. The multi-state competing risk model provides a relatively suitable solution for this problem. In this study, based on a previously published follow-up data set for prostate cancer patients, we developed traditional proportional hazard model, traditional competitive risk model, and multi-state competing risk model, respectively. By comparing the advantages and disadvantages of the three models with the same survival data, we clarified the clinical application value of the multi-state competitive risk model in survival data with multiple outcomes.