Purpose: We aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them. Methods: The main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses. Results: Results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64–0.84; p-value < 0.001). This finding was consistent with the results of the sensitivity analyses. Physical activities can help improve the protective effect of education against breast cancer, with relatively large mediation proportions. Education increases the risk of ER-positive breast cancer due to alterations in high-density lipoprotein level, triglyceride level, height, waist-to-hip ratio, body mass index, and smoking status, with relative medium mediation proportions. Other mediators including low-density lipoprotein, hip circumference, number of cigarettes smoked per day, time spent performing light physical activity, and performing vigorous physical activity for > 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%. Conclusion A low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.

Objective:To reevaluate the upper limit of normal (ULN) of serum alanine aminotransferase (ALT) by retrospectively analyzing the ALT levels in healthy people in Ningbo area.Methods:A total of 56 140 people who underwent health examination and detection of liver biochemical indexes in the Affiliated Hospital of Medical School of Ningbo University and Yinzhou Huamao Hospital of Ningbo from 2018 to 2020 were enrolled. After excluding relevant factors that may lead to liver injury, 11 411 people were included to compare the difference of serum ALT levels among different genders and age groups (20 to 29 years, 30 to 39 years, 40 to 49 years and 50 to 59 years) to determine the ALT ULN in different gender groups. Statistical methods were performed using two independent samples t test and analysis of variance. Results:The serum ALT of males was (19.20±7.90) U/L, which was higher than that of females ((13.75±6.17) U/L), with statistical significance ( t=41.16, P<0.001). The serum ALT ULN in males and in females were 35 U/L and 26 U/L, respectively. The serum ALT levels of 20 to 29, 30 to 39, 40 to 49 and 50 to 59 years old groups were (15.48±7.61) U/L, (16.21±7.40) U/L, (17.36±7.52) U/L and (18.77±7.57) U/L, respectively.The difference was statistically significant ( F=71.51, P<0.001). Serum ALT level in 50 to 59 years old group was higher than that in 20 to 29 years old group, and the difference was statistically significant ( t=13.11, P<0.01). In males, the ALT ULN of 20 to 29 years old was the lowest of 34.43 U/L, and highest of 35.29 U/L in 40 to 49 years old. In females, the ALT ULN in the 20 to 29 years old group was the lowest of 23.01 U/L, and the ALT ULN in the 50 to 59 years old group was the highest of 30.79 U/L. ALT ULN increased with age in females. The serum ALT of males was higher than that of females in all age groups ( t=29.55, 26.91, 13.43 and 4.62, respectively, all P<0.05). Conclusions:The serum ALT level is significantly correlated to gender and age. The serum ALT ULNs of healthy adult are 35 U/L in males and 26 U/L in females in Ningbo area.

Objective:To analyze the changing trend of intracerebral hemorrhage (ICH) incidence among residents with different characteristics during 9 years of comprehensive hypertension prevention and control (hypertension prevention and control) in Tengzhou from 2013 to 2021.Methods:From January 1, 2013 to December 31, 2021, the new ICH cases collected by the Center for Disease Control and Prevention in Tengzhou City were analyzed to calculate the incidence of ICH, and the trend of its distribution was analyzed among residents with different ages, sexes, and between urban and rural areas. The registered population information came from Tengzhou Public Security Bureau. Age and sex standardized incidence was calculated based on the 7th National Population Census in 2020. The Cochran-Armitage test was used to analyze the time and age trends of the incidence.Results:The overall ICH crude and standardized incidence in Tengzhou City decreased from 97.30/100 000 to 52.13/100 000 ( Z=-9.93, P<0.001) and 119.30/100 000 to 50.69/100 000 ( Z=-15.40, P<0.001) from 2013 to 2021, and both elevated to form a single peak in 2020, with 22.58% ( χ 2=24.02, P<0.001) and 18.09% ( χ 2=17.08, P<0.001) higher than in 2019, respectively. The trends in male and female incidence over the same period were similar to the overall trends, and the incidence was higher in males than in females in all years. The incidence of ICH increased with age in all years. The difference of increase in male incidence rate in 2020 was statistically significant in three age groups ≥45 years compared with 2019 (36.29%, 23.57% and 16.18%, respectively, χ 2=6.73, 4.65, 4.00, P<0.001). The incidence of ICH decreased by 70.07% and 36.23% ( Z=18.44, 5.22, P<0.001) in urban and rural areas respectively from 2013 to 2021, whereas increased by 34.15% ( χ 2=10.88, P<0.01) and 22.08% ( χ 2=18.63, P<0.001) in 2020 compared with 2019 separately. Conclusions:The incidence of ICH in Tengzhou from 2013 to 2021 showed a significant downward trend, with the decrease in the incidence of ICH in women exceeding that in men. The decrease in the incidence of ICH in urban areas exceeded that in rural areas, and male morbidity seemingly had a younger trend.

Objective:To investigate the temporal trend of the mortality rate of intracerebral hemorrhage (ICH) among residents with different characteristics during the comprehensive prevention and control of hypertension in Tengzhou, Shandong Province from 2013 to 2021.Methods:Comprehensive prevention and control of hypertension was conducted in Tengzhou, Shandong Province from 2013 to 2021. ICH mortality rate was calculated from January 1, 2013 to December 31, 2021. ICH mortality monitoring data from Tengzhou, Shandong Province was used to analyze the temporal trend of ICH mortality among residents with different characteristics. The registered residence population came from the Public Security Bureau of Tengzhou, Shandong Province. The age and gender standardized mortality rate was calculated based on the data of China's seventh population census in 2020. The temporal and age trends of mortality were analyzed using Cochran Armitage Trend Tests.Results:From 2013 to 2021, the overall crude and standardized mortality rates of ICH in Tengzhou, Shandong Province decreased from 50.51/100 000 and 63.21/100 000 to 17.51/100 000 and 16.74/100 000, respectively ( Z=-11.013 and -15.426, P<0.001), with an average annual mortality rate decrease of 12.41% and 15.30%, respectively. The overall crude and standardized mortality rates in 2017 peaked compared to 2016, mainly due to an increase of 32.94% and 30.92% in male ICH crude and standardized mortality rates, respectively ( χ2=12.328 and 15.854, P<0.05). The mortality rate of ICH increased with age, and the decreasing trend over time became increasingly evident with age. The mortality rate of ICH in the ≥65 year old age group decreased by 77.94% over 9 years ( Z=-14.065, P<0.001). In 2017, the mortality rate of ICH in the male age group ≥65 years old and female 45-54 years old increased by 31.13% and 125.79% compared to 2016 respectively, there were statistically significant differences ( χ2=8.877 and 5.421, P<0.05). In 2021, the mortality rates of urban and rural ICH decreased by 93.22% and 46.40% compared to 2013, respectively ( Z=-13.279 and -5.393, P<0.001), with an average annual decrease of 28.56% and 7.50%, respectively. The ICH mortality rate in rural areas increased by 30.54% in 2017 compared to 2016 ( χ2=16.086, P<0.001); after 2018, the mortality rate of ICH began to be higher than that of urban areas ( χ2=33.400 and 67.305, P<0.001). Conclusions:The ICH mortality rate in Tengzhou, Shandong Province has shown a significant downward trend over time, with male mortality rate higher than female mortality rate and rural mortality rate higher than urban areas. This suggests that the key attention should be paid to both male and rural areas.

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

Objective:To analyze the impact of hypertension prevention and control on the mortality rate of acute myocardial infarction (AMI) in Tengzhou City, Shandong Province from 2013 to 2021.Methods:This study was a cross-sectional study. The surveillance data of AMI deaths from January 1, 2013 (the time when hypertension prevention and control began in Tengzhou) to December 31, 2021 were collected in the coronary heart disease information management system, the mortality rate of AMI and its change trend were analyzed, and the distribution differences among residents with different characteristics were analyzed. The registered population information was obtained from Tengzhou Public Security Bureau, and the age and gender standardized mortality rate was calculated based on the data of the 7th national population census in 2020. The t test was used to compare the differences in blood pressure and laboratory items, chi-square test was used to compare the differences in mortality rate, and Cochran-Armitage trend test was used to compare the time trend and age trend of mortality rate, so as to analyze the impact of hypertension prevention and control on the mortality rate of AMI. Results:The overall crude and standardized AMI mortality rates in Tengzhou decreased from 50.87/100 000 and 63.82/100 000 to 41.08/100 000 and 38.70/100 000 from 2013 to 2021, respectively ( Z=-5.741, -10.884, both P<0.001), and double peaks were formed in 2014 and 2017. The first peak of crude and standardized mortality rate was formed in 2015 for males, which was 25.12% and 17.60% higher than that in 2013; and the first peak was formed in 2014 for females, which was 29.56% and 24.38% higher than that in 2013 ( χ2=13.200, 9.065, 14.862, 12.123) (all P<0.05). The second peaks of crude and standardized mortality were formed in 2017, with an increase of 18.17% and 17.17% for males and 25.73% and 22.34% for females from 2016 ( χ2=8.266, 9.182, 14.066, 11.105), the standardized mortality rate was 15.18%-29.01% higher in males than that in females ( χ2=6.239-19.326) (all P<0.05). The mortality rate of AMI increased with age ( Z=35.485-51.308) ( P<0.001). Compared with 2013, the mortality rate in males aged 55 to 64 years in 2015 increased by 64.29% from that in 2013, and that of females in 2017 increased by 108.48% from that in 2015; and that in females aged 35 to 44 years in 2016 increased by 373.51% from that in 2015 ( χ2=10.751, 12.805, 4.799); in 2021, the age group of male and female≥65 years decreased by 43.51% and 41.28% when compared with that in 2013, respectively ( Z=-7.333, -7.465) (all P<0.05). The mortality rate of AMI in urban areas decreased by 76.93% in 2021 when compared with that in 2016, and in rural areas it decreased by 30.28% than that in 2017. Both regions showed a downward trend ( Z=-7.560, -2.398) (both P<0.05). Conclusions:The mortality rate of AMI in Tengzhou City, Shandong Province from 2013 to 2021 shows a decreasing trend, and prevention and control of hypertension may be one of the reasons. The standardized mortality rate of males is higher than that of females, and the mortality rate decline rate in rural areas is lower than that in urban areas. The primary and secondary prevention of AMI in such populations should be strengthened.

Objective:To explore the causal associations of two blood pressure phenotype and four lipid fractions with type 2 diabetes mellitus(T2DM) in European and East Asian populations using Two-Sample Mendelian randomization analysis.Methods:Blood pressure phenotype, lipid fractions and T2DM genetic loci from two ethnics were matched and combined according to single nucleotide polymorphisms(SNPs) numbering. With SNPs closely related to the exposure phenotype as instrumental variables, the inverse variance weighting method was used to analyze the causal effects of blood pressure phenotype and lipid fractions on T2DM in different ethnic groups. The sensitivity analysis was conducted using MR-Egger regression model, Weighted Median method, MR-PRESSO, MR-robust Adjusted Profile Score, and leave-one-out method.Results:Among European populations, systolic blood pressure( OR=1.40, 95% CI 1.23-1.59, P<0.001) and diastolic blood pressure( OR =1.24, 95% CI 1.08-1.42, P=0.002)were associated with increased risk of T2DM while high density lipoprotein-cholesterol( OR=0.68, 95% CI 0.62-0.76, P<0.001) reduced the risk of T2DM. In East Asian ethnicity, elevated diastolic blood pressure( OR=0.75, 95% CI 0.59-0.95, P=0.007) reduced the risk of T2DM. Sensitivity analysis confirmed the results. Conclusion:There are differences in the effects of blood pressure phenotype and lipid composition on T2DM in different ethnic groups, which may be related to population heterogeneity and exposure sensitivity. It should be taken into consideration in extrapolation.

Objective:To examine treatment outcomes of breast phyllodes tumors and the prognosis factors of local recurrence.Methods:This retrospective cohort study included 276 patients who underwent surgical resection at Breast Center, Peking University People′s Hospital from January 2011 to December 2019. Tumor subtype and histopathological features were determined from pathology reports, and the deadline of follow-up was September 30 th, 2020. All 276 patients underwent open surgery, including 17 patients of mastectomy, and 259 patients of lumpectomy. The enrolled patients were all female, with age of (41.5±11.3) years (rang: 11 to 76 years), and tumor diameter of 35(28) mm ( M( Q R)). The Kaplan-Meier method and Log-rank test were used for survival analysis. The multivariate analysis was implemented using the Cox proportional hazard model. Results:According the pathologic test, there were 191 patients of benign phyllodes tumor, 67 patients of borderline tumor and 18 patients of malignant tumor. There were 249 patients with a follow-up of more than 6 months, and 14.1% (35/249) had local recurrence. The time-to-recurrence was (28.6±22.2) months (range: 2 to 96 months), (29.1±18.1) months (range: 2 to 80 months), (32.1±30.1) months (range: 5 to 96 months) and (12.0±6.9) months (range: 8 to 20 months) for benign, borderline and malignant phyllodes tumors. Tumor diameter (≥100 mm vs.<50 mm, HR=3.968, 95%CI: 1.550 to 10.158, P=0.004) and malignant heterologous element (yes vs. no, HR=26.933, 95%CI: 3.105 to 233.600, P=0.003) were prognosis factors of local recurrence. One death from malignant phyllodes occurred after distant metastasis. The 3-year disease-free survival rates of benign, borderline and malignant phyllodes tumor were 88.2%, 81.7% and 81.4% ( P=0.300). Conclusion:Phyllodes tumors have a considerable local recurrence rate, which may be associated with tumor diameter and malignant heterologous element.