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.

Abstract: Objective To analyze the epidemiological characteristics of reported cases of dengue fever in mainland China from 2019 to 2023 and provide a scientific basis for dengue prevention and control efforts. Methods The temporal, spatial, and population distribution characteristics, as well as the trends of dengue fever cases reported in the National Notifiable Disease Reporting System (NNDRS) of China were analyzed using software such as Joinpoint regression, SaTScan, and ArcGIS. Results From 2019 to 2023, a total of 43 095 cases were reported in China, with an average incidence rate of 61/100 000. The annual reported incidence rate fluctuated significantly (AAPC=-3.16%, 95%CI:-54.16%-91.47%), mainly concentrated in 2019 and 2023, accounting for 96.83% of the total reported cases over the past five years. All age groups were susceptible to the disease, with the 30 to <40 age group comprising 22.6% of cases. Cases were reported throughout the year, with a rapid increase starting in June and a peak period concentrated between August and October (n=34 780, RR=12.44, LLR=29 262.52, P<0.05). The epidemic was primarily characterized by imported cases leading to autochthonous transmission, with the majority of imported cases originating from Southeast Asia (86.56%), particularly from Cambodia (46.11%, 3 284 cases) and Myanmar (25.99%, 1 851 cases). The epidemic characteristics varied significantly across different years, with high risks of autochthonous transmission epidemics in Southwest, South, and Southeast China. High-risk local transmission were mainly distributed in Yunnan and Guangdong. The duration of the peak period of the epidemic was affected by the timeliness of early detection of local transmission, and the peak value of the epidemic was related to the effectiveness of prevention and control measures. The scale of the epidemic was influenced by the pressure of by cross-border transmission and the ability to implement local measures for dengue prevention and control. Conclusions With the increasing trend of global dengue transmission, the risk of autochthonous transmission of dengue in China is rising. It is recommended to strengthen proactive early outbreak surveillance, along with well preparation of personnel, technology, and resources for dengue prevention and control.According to autochthonous conditions, reasonable management and risk assessment of cross-border travelers should be explored to effectively.

OBJECTIVE: To analyze the epidemiological characteristics of measles, mumps, and rubella (MMR) between 2014 and 2021 and identify potential strategies and measures for the prevention and control of MMR in China. METHODS: Data on MMR was obtained from China's National Notifiable Disease Reporting System for the period from 2014 to 2021. Spatiotemporal distributions were analyzed using SaTScan; temporal trends were analyzed using JoinPoint; and clusters were visualized using ArcGIS. RESULTS: A total of 1,808,067 cases of MMR were reported from 2014 to 2021 in China's mainland, most of which were children and students under the age of 20. The incidence of measles declined during 2014-2021, whereas that of mumps and rubella peaked in 2019. MMR-reported cases generally peaked from March to July; however, high numbers of mumps cases were reported from September to November in 2020-2021. Measles and rubella clusters predominantly occurred in Western China, whereas clusters of mumps were generally found in the southern region. CONCLUSION The relatively heterogeneous epidemiological characteristics of MMR have highlighted the weaknesses and gaps in surveillance and timely control of MMR transmission in China's mainland. Real-time and intelligent monitoring data should be collected for evidence-based early interventions.
China/epidemiology* ; Humans ; Measles/epidemiology* ; Child ; Mumps/epidemiology* ; Adolescent ; Child, Preschool ; Rubella/epidemiology* ; Young Adult ; Infant ; Male ; Female ; Adult ; Incidence ; Middle Aged ; Measles-Mumps-Rubella Vaccine ; Infant, Newborn

Objective To construct an evaluation index system for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept, so as to provide insights into the control and elimination of mountain-type zoonotic visceral leishmaniasis using the One Health approach. Methods A preliminary evaluation index system was constructed based on literature review, panel discussions and field surveys. Thirty-three experts were selected from 7 provincial disease control and prevention centers in Beijing Municipality, Hebei Province, Shanxi Province, Henan Province, Sichuan Province, Shaanxi Province and Gansu Province where mountain-type zoonotic visceral leishmaniasis was endemic, and two rounds of expert consultations were conducted to screen the indicators. The positive coefficient, degree of concentration, degree of coordination, and authority of the experts were calculated, and the normalized weights of each index were calculated with the analytic hierarchy process. Results The response rates of questionnaires during two rounds of expert consultation were both 100.00% (33/33), and the authority coefficients of the experts were 0.86 and 0.88, respectively. The coefficients of coordination among experts on the rationality, importance, and operability of the indicators were 0.392, 0.437, 0.258, and 0.364, 0.335, 0.263, respectively (all P values < 0.05). Following screening, the final evaluation index system included 3 primary indicators, 17 secondary indicators, and 50 tertiary indicators. The normalized weights of primary indicators “external environment”, “internal support” and “comprehensive control” were 16.98%, 38.73% and 44.29%, respectively. Among the secondary indicators of the primary indicator “external environment”, the highest weight was seen for natural environment (66.67%), and among the secondary indicators of the primary indicator “internal support”, the lowest weight was seen for the scientific research for visceral leishmaniasis control (8.26%), while other indicators had weights of 12.42% to 13.38%. Among the secondary indicators of the primary indicator “comprehensive control”, the weight was 16.67% for each indicator. Conclusions An evaluation index system has been constructed for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept. In addition to assessment of the effect of conventional mountain-type zoonotic visceral leishmaniasis control measures, this index system integrates the importance of top-level design, organizational management, and implementation of control measures, and includes indicators related to multi-sectoral cooperation.

Objective:To investigate the changes in structural brain network topology and microstructural damage in patients with multiple sclerosis (MS), and to analyze its correlation with cognitive function.Methods:Clinical and imaging data of 114 patients with MS (MS group) diagnosed in the First Affiliated Hospital of Chongqing Medical University from May 2021 to September 2022 were analyzed retrospectively. In addition, 71 volunteers were recruited as a healthy control group (HC group) during the same period. All subjects were performed on cognitive assessment and 3D-T 1 magnetization-prepared rapid gradient echo, 3D-fluid-attenuated inversion recovery, and diffusion kurtosis imaging (DKI) scans. GRETNA software was used to obtain network topology attributes, and global attributes included global efficiency, local efficiency, and small-world attributes [clustering coefficient(Cp), shortest path length(Lp), normalized Cp(γ), normalized Lp, and small-world index (σ)]. Local attributes included betweenness centrality (BC), degree centrality (DC), nodal clustering coefficient (NCp), nodal efficiency, nodal local efficiency (NLe) and nodal shortest path length. The DKI parameter map generated by the post-processing software was used to extract the DKI parameter values of the brain region with abnormal local topology of the brain structure network. The differences of global attributes, local attributes and DKI parameter values [kurtosis fractional anisotropy (KFA), mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) values] were analyzed by independent sample t-test or Mann-Whitney U test, and corrected by false discovery rate (FDR). Spearman or Pearson correlation analysis was used to evaluate the correlation between abnormal brain structure network topology attributes and cognitive scale scores in the MS group. Results:Both the MS group and the HC group structure network showed small-world attributes, and the γ and σ values of the MS group were significantly lower than those in the HC group (FDR correction, P<0.05). Compared with the HC group, BC, DC, NCp and NLe broadly reduced in the MS group, mainly involving in bilateral frontal, temporal, precuneus, amygdala, and thalamus (FDR correction, P<0.05). After FDR correction, compared with the HC group, the KFA, MK, RK and AK values of 23 brain regions with abnormal local attributes of the network in the MS group were significantly changed in several brain regions (FDR correction, P<0.05). The correlation analysis showed, after FDR correction, the DC value of the right putamen in MS patients was positively correlated with the digit span test (DST) scores ( r=0.318 ,P=0.001). Conclusion:There are extensive changes in the structural brain network of MS patients, accompanied by varying degrees of microstructural damage, and the reduction of degree centrality in the basal ganglia putamen region is associated with cognitive impairment.

Objective:To verify the prognostic significance of the tumor regression grade (TRG) for muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC) after neoadjuvant chemotherapy.Methods:The data of 70 MIBC patients treated with gemcitabine combined with cisplatin neoadjuvant chemotherapy and RC in Sun Yat-sen University Cancer Center between July 2016 to November 2021 were retrospectively reviewed. There were 65 males and 5 females, with an average age(59.79±10.56)years old. The patients accepted transurethral resection of bladder tumor (TURBT) specimens before neoadjuvant chemotherapy. Clinicopathological characteristics of patients were recorded and TRG was assessed. TRG evaluation criteria: TRG 1 was defined as no cancer residue, TRG 2 was defined as the proportion of residual cancer area to tumor bed area <50%, and TRG 3 was defined as the proportion of residual cancer area to the area of the tumor bed ≥ 50%. Chi-square test or Fisher's exact test were used to compare the relationship between patients' clinicopathological characteristics and TRG. The relationship between post-neoadjuvant therapy tumor and node(ypTN)stage, and survival, including overall survival(OS)and recurrence-free survival (RFS) were analyzed by Kaplan-Meier analysis. The pathologically locally descending disease was defined as (ypT < T 2 and ypN=N 0) and pathologically locally advanced disease was defined as (ypT≥T 2 and/or ypN ≥N 1). Cox regression was used for univariate and multivariate analysis of OS and RFS. Results:Chi-square test or Fisher exact test analysis showed TRG was significantly associated with ypT stage ( P < 0.001), ypN stage ( P = 0.002), lympho-vascular invasion ( P<0.001) and variant histology ( P<0.001). The OS of patients with TRG 1, TRG 2 and TRG 3 were 20.5(10.3, 31.8), 17.0(11.0, 30.8)and 15.0(11.0, 26.0) months, respectively, and the difference was significantly different( P = 0.037). The RFS of patients with TRG 1, TRG 2 and TRG 3 were 15.0(8.3, 25.5), 15.0(8.0, 27.0)and 11.0(4.5, 25.5) months, respectively, and the difference was significantly different ( P=0.029). There were significant differences between patients with pathologically locally descending disease and locally advanced disease in OS [18.5(10.3, 30.8)vs.15.0(11.0, 27.3)months, P = 0.013] and RFS [14.0(8.0, 24.0)vs. 11.5(8.0, 26.8)months, P = 0.012]. Among patients with locally advanced pathology, the OS was 19.5(11.0, 32.5)months for patients with TRG ≤2, 13.5(10.8, 26.0)months for patients with TRG 3( P=0.140). The RFS was 12.0(8.0, 31.0)months for those patients with TRG ≤2 and 11.0(6.0, 26.0)months for those patients with TRG 3( P = 0.180). Cox univariate analyses showed that patients with TRG 3 were associated with decreased OS ( HR = 6.043, 95% CI 1.170-31.213, P = 0.032) and RFS ( HR = 6.354, 95% CI 1.231-31.802, P = 0.027). Conclusions:This study showed that TRG was correlated with OS and RFS among patients. The patients who had the higher TRG had the worse prognosis. It was confirmed that TRG predicted the prognosis of patients undergoing radical cystectomy after neoadjuvant chemotherapy. Therefore, TRG assessment is recommend in pathology report for patients who had radical cystectomy after neoadjuvant chemotherapy.

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.