Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

Climate change is a significant environmental concern in the 21^st century. It can directly and indirectly affect public health, making it a major public health problem. This review focused on the relationship between meteorological factors and health-related behaviors such as physical activity, sleep, dietary behavior, and social contact behavior. The results indicated that meteorological factors such as temperature, relative humidity, wind speed, atmospheric pressure, and rainfall are associated with the four health behaviors. Physical activity levels are negatively associated with temperature, relative humidity, and rainfall. Sleep quality tends to decrease under extreme temperatures and extreme weather events. Dietary behavior is influenced by high and low temperatures, low pressure, and daylight duration, which in turn affects appetite and food intake. Social contact frequency decreases in response to extreme temperatures, increased rainfall, and extreme weather events. However, there are differences in the strength and direction of the associations between meteorological factors and health-related behaviors in various studies. Research on the combined effects of multiple meteorological factors exposure on health-related behaviors is rare, and the mechanisms underlying the associations are unclear. Therefore, there is a need for more multi-center, large-scale studies to explore the biological and behavioral mechanisms behind these associations, which will help clarify the complex effects of meteorological factors on human health behaviors and provide scientific evidence for policy-making, thereby mitigating the negative impact of climate change on public health.

[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0～74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80～84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23％,P＜0.001),ASMRC showed a marginal increase(AAPC=0.78％,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.

Objective To explore the mechanism by which Liqi Huoxue Dripping Pill(LQHXDP)inhibits cardiomyocyte apoptosis in rats with myocardial ischemia-reperfusion injury(MIRI).Methods Male Sprague-Dawley(n=96)rats were randomly assigned to a normal,sham-operated,model,LQHXDP,adenovirus negative control(Ad-shNC),adenovirus-mediated HIF-1α knockdown(Ad-shHIF-1α),LQHXDP+Ad-shNC,or LQHXDP+Ad-shHIF-1α group using a random number table.LQHXDP was administered daily via oral gavage at 175.0 mg/(kg·d)for 10 consecutive days.On day 7,recombinant adenovirus was injected into the left ventricular wall of rats in the corresponding groups at multiple points.On day 10,the MIRI model was established by ligating the left anterior descending coronary artery.The sham-operated group underwent thoracotomy and suture placement without coronary ligation.Samples were collected after reperfusion was completed.Serum creatine kinase isoenzymes(CK-MB),cardiac troponin I(cTnI),and heart-type fatty acid binding protein(H-FABP)levels were measured using enzyme-linked immunosorbent assay.2,3,5-Triphenyltetrazolium chloride staining was used to measure the volume ratio of myocardial infarction.HE staining was performed to observe the morphology of myocardial tissue.Terminal transferase uridyl nick end labeling assay was conducted to analyze the apoptosis rate of cardiomyocytes,and Western blotting was used to detect the expression of key proteins in the apoptosis(B-cell lymphoma-2[Bcl-2],Bcl-2 associated X protein[Bax],and cleaved cysteinyl aspartate specific proteinase 3[Cleaved-Caspase-3]and HIF-1α/Bcl-2-adenovirus E1B 19 kDa interacting protein 3(BNIP3)signaling pathway(HIF-1α,heme oxygenase-1[HO-1],and BNIP3).Results LQHXDP pretreatment significantly reduced serum CK-MB,cTnI,and H-FABP levels,as well as the myocardial infarction volume ratio in rats with MIRI.LQHXDP also improved myocardial tissue morphology,decreased cardiomyocyte apoptosis,upregulated Bcl-2 protein expression,and downregulated Bax,Cleaved-Caspase-3,HIF-1α,HO-1,and BNIP3 protein expressions(P<0.05).However,adenovirus-mediated shRNA HIF-1α impaired the effects of LQHXDP pretreatment in attenuating myocardial injury and inhibiting apoptosis in MIRI rats(P<0.05).Conclusion LQHXDP reduces cardiomyocyte apoptosis and protects rat myocardium from MIRI by regulating the HIF-1α/BNIP3 signaling pathway.

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.

The incidence rate of suspected adverse events following immunization (AEFI) after single administration of pentavalent recombinant rotavirus attenuated live vaccine (RV5) in Chaoyang District, Beijing City from 2019 to 2021 was 362.3 per 100 000 doses. The incidence rate of AEFI after simultaneous administration with oral polio vaccine (OPV), inactivated polio vaccine (IPV), hepatitis B vaccine (HBV), Haemophilus influenzae type b (Hib), and pneumococcal conjugate vaccine 13-valent (PCV13) was 239.3 per 100 000, 643.4 per 100 000, 346.8 per 100 000, 438.1 per 100 000, and 434.0 per 100 000, respectively. The specific incidence rates for common AEFI symptoms such as fever, local allergic rash, irritability, and vomiting under different vaccination regimens were as follows: RV5 alone (fever: 88.3 per 100 000, rash: 9.1 per 100 000, irritability: 100.5 per 100 000, vomiting: 83.3 per 100 000), RV5 and IPV simultaneous administration (fever: 239.4 per 100 000, rash: 104.7 per 100 000, irritability: 134.7 per 100 000, vomiting: 89.8 per 100 000), RV5 and OPV simultaneous administration (fever: 119.6 per 100 000, rash: 32.6 per 100 000, irritability: 32.6 per 100 000, vomiting: 32.6 per 100 000), RV5 and HBV simultaneous administration (fever: 111.0 per 100 000, rash: 69.4 per 100 000, irritability: 83.2 per 100 000, vomiting: 41.6 per 100 000), RV5 and Hib simultaneous administration (fever: 159.3 per 100 000, rash: 238.9 per 100 000, irritability: 0 per 100 000, vomiting: 39.8 per 100 000), and RV5 and PCV13 simultaneous administration (fever: 142.8 per 100 000, rash: 98.0 per 100 000, irritability: 126.0 per 100 000, vomiting: 25.2 per 100 000).

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.

The incidence rate of suspected adverse events following immunization (AEFI) after single administration of pentavalent recombinant rotavirus attenuated live vaccine (RV5) in Chaoyang District, Beijing City from 2019 to 2021 was 362.3 per 100 000 doses. The incidence rate of AEFI after simultaneous administration with oral polio vaccine (OPV), inactivated polio vaccine (IPV), hepatitis B vaccine (HBV), Haemophilus influenzae type b (Hib), and pneumococcal conjugate vaccine 13-valent (PCV13) was 239.3 per 100 000, 643.4 per 100 000, 346.8 per 100 000, 438.1 per 100 000, and 434.0 per 100 000, respectively. The specific incidence rates for common AEFI symptoms such as fever, local allergic rash, irritability, and vomiting under different vaccination regimens were as follows: RV5 alone (fever: 88.3 per 100 000, rash: 9.1 per 100 000, irritability: 100.5 per 100 000, vomiting: 83.3 per 100 000), RV5 and IPV simultaneous administration (fever: 239.4 per 100 000, rash: 104.7 per 100 000, irritability: 134.7 per 100 000, vomiting: 89.8 per 100 000), RV5 and OPV simultaneous administration (fever: 119.6 per 100 000, rash: 32.6 per 100 000, irritability: 32.6 per 100 000, vomiting: 32.6 per 100 000), RV5 and HBV simultaneous administration (fever: 111.0 per 100 000, rash: 69.4 per 100 000, irritability: 83.2 per 100 000, vomiting: 41.6 per 100 000), RV5 and Hib simultaneous administration (fever: 159.3 per 100 000, rash: 238.9 per 100 000, irritability: 0 per 100 000, vomiting: 39.8 per 100 000), and RV5 and PCV13 simultaneous administration (fever: 142.8 per 100 000, rash: 98.0 per 100 000, irritability: 126.0 per 100 000, vomiting: 25.2 per 100 000).

[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0～74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80～84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23％,P＜0.001),ASMRC showed a marginal increase(AAPC=0.78％,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.

Objective To explore the mechanism by which Liqi Huoxue Dripping Pill(LQHXDP)inhibits cardiomyocyte apoptosis in rats with myocardial ischemia-reperfusion injury(MIRI).Methods Male Sprague-Dawley(n=96)rats were randomly assigned to a normal,sham-operated,model,LQHXDP,adenovirus negative control(Ad-shNC),adenovirus-mediated HIF-1α knockdown(Ad-shHIF-1α),LQHXDP+Ad-shNC,or LQHXDP+Ad-shHIF-1α group using a random number table.LQHXDP was administered daily via oral gavage at 175.0 mg/(kg·d)for 10 consecutive days.On day 7,recombinant adenovirus was injected into the left ventricular wall of rats in the corresponding groups at multiple points.On day 10,the MIRI model was established by ligating the left anterior descending coronary artery.The sham-operated group underwent thoracotomy and suture placement without coronary ligation.Samples were collected after reperfusion was completed.Serum creatine kinase isoenzymes(CK-MB),cardiac troponin I(cTnI),and heart-type fatty acid binding protein(H-FABP)levels were measured using enzyme-linked immunosorbent assay.2,3,5-Triphenyltetrazolium chloride staining was used to measure the volume ratio of myocardial infarction.HE staining was performed to observe the morphology of myocardial tissue.Terminal transferase uridyl nick end labeling assay was conducted to analyze the apoptosis rate of cardiomyocytes,and Western blotting was used to detect the expression of key proteins in the apoptosis(B-cell lymphoma-2[Bcl-2],Bcl-2 associated X protein[Bax],and cleaved cysteinyl aspartate specific proteinase 3[Cleaved-Caspase-3]and HIF-1α/Bcl-2-adenovirus E1B 19 kDa interacting protein 3(BNIP3)signaling pathway(HIF-1α,heme oxygenase-1[HO-1],and BNIP3).Results LQHXDP pretreatment significantly reduced serum CK-MB,cTnI,and H-FABP levels,as well as the myocardial infarction volume ratio in rats with MIRI.LQHXDP also improved myocardial tissue morphology,decreased cardiomyocyte apoptosis,upregulated Bcl-2 protein expression,and downregulated Bax,Cleaved-Caspase-3,HIF-1α,HO-1,and BNIP3 protein expressions(P<0.05).However,adenovirus-mediated shRNA HIF-1α impaired the effects of LQHXDP pretreatment in attenuating myocardial injury and inhibiting apoptosis in MIRI rats(P<0.05).Conclusion LQHXDP reduces cardiomyocyte apoptosis and protects rat myocardium from MIRI by regulating the HIF-1α/BNIP3 signaling pathway.