A novel correction method for modelling parameter-driven autocorrelated time series with count outcome.

BACKGROUND: Count time series (e.g., daily deaths) are a very common type of data in environmental health research. The series is generally autocorrelated, while the widely used generalized linear model is based on the assumption of independent outcomes. None of the existing methods for modelling parameter-driven count time series can obtain consistent and reliable standard error of parameter estimates, causing potential inflation of type I error rate. METHODS: We proposed a new maximum significant ρ correction (MSRC) method that utilizes information of significant autocorrelation coefficient ρ estimate within 5 orders by moment estimation. A Monte Carlo simulation was conducted to evaluate and compare the finite sample performance of the MSRC and classical unbiased correction (UB-corrected) method. We demonstrated a real-data analysis for assessing the effect of drunk driving regulations on the incidence of road traffic injuries (RTIs) using MSRC in Shenzhen, China. Moreover, there is no previous paper assessing the time-varying intervention effect and considering autocorrelation based on daily data of RTIs. RESULTS: Both methods had a small bias in the regression coefficients. The autocorrelation coefficient estimated by UB-corrected is slightly underestimated at high autocorrelation (≥ 0.6), leading to the inflation of the type I error rate. The new method well controlled the type I error rate when the sample size reached 340. Moreover, the power of MSRC increased with increasing sample size and effect size and decreasing nuisance parameters, and it approached UB-corrected when ρ was small (≤ 0.4), but became more reliable as autocorrelation increased further. The daily data of RTIs exhibited significant autocorrelation after controlling for potential confounding, and therefore the MSRC was preferable to the UB-corrected. The intervention contributed to a decrease in the incidence of RTIs by 8.34% (95% CI, -5.69-20.51%), 45.07% (95% CI, 25.86-59.30%) and 42.94% (95% CI, 9.56-64.00%) at 1, 3 and 5 years after the implementation of the intervention, respectively. CONCLUSIONS: The proposed MSRC method provides a reliable and consistent approach for modelling parameter-driven time series with autocorrelated count data. It offers improved estimation compared to existing methods. The strict drunk driving regulations can reduce the risk of RTIs.

[Anti-tumor mechanism of total saponins of Paridis Rhizoma on inducing ferroptosis of breast cancer MCF-7 cells].

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.

The Effectiveness of National Expanded Program on Immunization With Hepatitis A Vaccines in the Chinese Mainland: Interrupted Time-Series Analysis.

BACKGROUND: The high prevalence of hepatitis A delivered a blow to public health decades ago. The World Health Organization (WHO) set a goal to eliminate viral hepatitis including hepatitis A by 2030. In 2008, hepatitis A vaccines were integrated into the Expanded Program on Immunization (EPI) in China to alleviate the burden of hepatitis A, although the effectiveness of the EPI has not been well investigated. OBJECTIVE: We aimed to evaluate the intervention effect at both provincial and national levels on the incidence of hepatitis A in the Chinese mainland from 2005 to 2019. METHODS: Based on the monthly reported number of hepatitis A cases from 2005 to 2019 in each provincial-level administrative division, we adopted generalized additive models with an interrupted time-series design to estimate province-specific effects of the EPI on the incidence of hepatitis A among the target population (children aged 2-9 years) from 2005 to 2019. We then pooled province-specific effect estimates using random-effects meta-analyses. We also assessed the effect among the nontarget population and the whole population. RESULTS: A total of 98,275 hepatitis A cases among children aged 2-9 years were reported in the Chinese mainland from 2005 to 2019, with an average annual incidence of 5.33 cases per 100,000 persons. Nationally, the EPI decreased the hepatitis A incidence by 80.77% (excess risk [ER] -80.77%, 95% CI -85.86% to -72.92%) during the study period, guarding an annual average of 28.52 (95% empirical CI [eCI] 27.37-29.00) cases per 100,000 persons among the target children against hepatitis A. Western China saw a more significant effect of the EPI on the decrease in the incidence of hepatitis A among the target children. A greater number of target children were protected from onset in Northwest and Southwest China, with an excess incidence rate of -129.72 (95% eCI -135.67 to -117.86) and -66.61 (95% eCI -67.63 to -64.22) cases per 100,000 persons on average, respectively. Intervention effects among nontarget (ER -32.88%, 95% CI -39.76% to -25.21%) and whole populations (ER -31.97%, 95% CI -39.61% to -23.37%) were relatively small. CONCLUSIONS: The EPI has presented a lasting positive effect on the containment of hepatitis A in the target population in China. The EPI's effect on the target children also provided a degree of indirect protection for unvaccinated individuals. The continuous surveillance of hepatitis A and the maintenance of mass vaccination should shore up the accomplishment in the decline of hepatitis A incidence to ultimately achieve the goal set by the WHO.