Objective: To investigate the trends in mortality and life loss of gastric cancer in Wenzhou City, Zhejiang Province from 2014 to 2023, so as to provide the evidence for formulating the prevention and control strategy for gastric cancer. Methods: The surveillance on causes of death data of permanent residents in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2014 to 2023. The crude mortality of gastric cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL) and rate of potential years of life lost (PYLLR). The characteristics of mortality and life loss of gastric cancer in different genders and age groups were described. The trends in mortality and PYLLR of gastric cancer were analyzed using the average annual percent change (AAPC). Results: Totally 17 080 deaths were reported due to gastric cancer in Wenzhou City from 2014 to 2023, accounting for 12.58% and ranking third in the order of malignant tumor deaths. The crude mortality of gastric cancer was 20.73/105, and the standardized mortality was 15.22/105, showing decreasing trends (AAPC=-3.311%, -6.470%, both P<0.05). The crude mortality of gastric cancer was 29.22/105 in men and 11.61/105 in women, with standardized mortality rates of 20.81/105 and 8.74/105 (both P<0.05). The crude mortality of gastric cancer appeared a tendency towards a rise with increasing age (P<0.05), reaching the highest rate of 225.88/105 in the group aged 80 to <85 years. The PYLL and PYLLR of gastric cancer were 107 607.50 person-years and 1.37‰. The PYLLR appeared a tendency towards a decline from 2014 to 2023, with AAPC of -6.667% (P<0.05). Conclusions The mortality and PYLLR of gastric cancer in Wenzhou City appeared a tendency towards a decline from 2014 to 2023. Men and the elderly populations were the key groups for the prevention and treatment of gastric cancer.

Objective: To investigate the trends in mortality and life loss due to falls among the elderly in Wenzhou City, Zhejiang Province, so as to provide the basis for formulating prevention and control measures for falls among the elderly. Methods: The data on fall-related deaths among the elderly aged 60 and above in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2015 to 2023. The crude mortality was calculated and standardized using the data from the Sixth National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL), average years of life lost (AYLL), and potential years of life lost rate (PYLLR). The trends in mortality and life loss among the elderly were analyzed using the annual percent change (APC) and average annual percent change (AAPC). Results: There were 11 378 deaths due to falls among the elderly in Wenzhou City from 2015 to 2023, with a crude mortality of 82.67/100 000 and a standardized mortality of 65.32/105, which appeared no significant changing trend (AAPC=3.401%、2.995%,both P>0.05). There was a tendency towards a rise from 2019 to 2023 (APC=12.592%、11.507%, both P<0.05). The majority of falls occurred at home, with 6 312 cases accounting for 55.48%. The primary types of fall-related deaths were slips, trips, and falls on the same level, with 8 541 cases representing 75.07%. The crude mortality and standardized mortality of falls in males were 76.63/105 and 60.86/105, which were lower than that in females at 88.72/100 000 and 70.33/100 000 (both P<0.05), and the trends were consistent with the overall population. The crude mortality of falls among the elderly increased with age (P<0.05). From 2015 to 2023, the crude mortality of falls among the elderly aged 60 to <65 years showed an upward trend (AAPC=4.860%, P<0.05), while no significant trend was observed in other age groups (all P>0.05). The PYLL was 5 123 person-years, the AYLL was 0.45 years per person, and the PYLLR was 0.37‰. From 2015 to 2023, PYLL showed an upward trend (AAPC=5.477%, P<0.05). The PYLL, AYLL, and PYLLR for males were 3.08 times, 3.48 times, and 2.67 times those of females, respectively. Conclusions From 2015 to 2023, the mortality of falls among the elderly in Wenzhou City had remained relatively stable. However, PYLL showed an upward trend. Males and older seniors were key groups for falls prevention. It is recommended to enhance health education and promote age-friendly home modifications to prevent falls among the elderly.

Objective To explore the mechanism of Angong Niuhuang pill on the neurological function of rats with spontaneous intracerebral hemorrhage based on the tumor necrosis factor-α/nuclear factor-κB(TNF-α/NF-κB)signaling pathway combined with network pharmacology.Methods The targets for treatment of intracerebral hemorrhage with Angong Niuhuang pill were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),High-Throughput Experiment and Refeence-guided Database of Traditional Chinese Medicine(HERB).Key targets were screened for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and molecular docking.Then,rats were randomly divided into normal control group,model group,Angong Niuhuang pill group(administered by gavage at 270 mg·kg-1·d-1),and the Western medicine group(intraperitoneal injection of 4 500 mg·kg-1·d-1+furosemide 1.8 mg·kg-1·d-1),the dosage administered was the equivalent dose ratio calculated based on the body surface area for humans and animals.The intracerebral hemorrhage model was replicated by the autologous heart blood caudate nucleus injection method.After modeling,the neurological function behavior scores,brain tissue water content,pathological changes of brain tissue,blood-brain barrier permeability,and protein expression levels of NF-κB p65,tumor necrosis factor receptor 1(TNFR1),inhibitor NF-κBα(IκBα)and TNF-α in brain tissue of each group were observed.Results A total of 216 intersection genes were selected.The results of GO enrichment analysis and KEGG pathway annotation analysis predicted that the TNF-α/NF-κB inflammatory signaling pathway was one of the main regulatory pathways.The animal experiment results showed that at 72 hours after modeling,compared with the model group,the neurological function score,brain tissue water content,and blood-brain barrier permeability index evans blue(EB)content of the Angong Niuhuang pill group were significantly decreased[neurological function score:1.62±0.62 vs.2.23±0.58,brain water content:(77.7±0.49)%vs.(79.9±0.04)%,EB content(μg/L):490.50±100.79 vs.1 966.20±94.81,all P<0.05];the pathological observation of brain tissue showed that Angong Niuhuang pill could reduce the pathological damage of brain tissue around the hematoma,repair the blood-brain barrier,and alleviate brain edema;the Western blotting results showed that Angong Niuhuang pill could inhibit the protein expression of TNF-α,TNFR1,and NF-κB p65 in brain tissue[NF-κB p65 protein expresion(NF-κB p65/β-actin):2.27±0.52 vs.5.40±0.26;TNFR1 protein expression(TNFR1/β-actin):1.49±0.33 vs.2.52±0.04,TNF-α protein expression(TNF-α/β-actin):1.40±0.13 vs.2.29±0.18,all P<0.05],promote the protein expression of IκB-α(IκB-α/β-actin):0.78±0.02 vs.0.32±0.00,P<0.05).Conclusion Angong Niuhuang pill may regulate the TNF-α/NF-κB signaling pathway by inhibiting the expression of TNFR1 and promoting the expression of IκB-α,exerting neuroprotective effects.

Objective To explore the mechanism of Angong Niuhuang pill on the neurological function of rats with spontaneous intracerebral hemorrhage based on the tumor necrosis factor-α/nuclear factor-κB(TNF-α/NF-κB)signaling pathway combined with network pharmacology.Methods The targets for treatment of intracerebral hemorrhage with Angong Niuhuang pill were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),High-Throughput Experiment and Refeence-guided Database of Traditional Chinese Medicine(HERB).Key targets were screened for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and molecular docking.Then,rats were randomly divided into normal control group,model group,Angong Niuhuang pill group(administered by gavage at 270 mg·kg-1·d-1),and the Western medicine group(intraperitoneal injection of 4 500 mg·kg-1·d-1+furosemide 1.8 mg·kg-1·d-1),the dosage administered was the equivalent dose ratio calculated based on the body surface area for humans and animals.The intracerebral hemorrhage model was replicated by the autologous heart blood caudate nucleus injection method.After modeling,the neurological function behavior scores,brain tissue water content,pathological changes of brain tissue,blood-brain barrier permeability,and protein expression levels of NF-κB p65,tumor necrosis factor receptor 1(TNFR1),inhibitor NF-κBα(IκBα)and TNF-α in brain tissue of each group were observed.Results A total of 216 intersection genes were selected.The results of GO enrichment analysis and KEGG pathway annotation analysis predicted that the TNF-α/NF-κB inflammatory signaling pathway was one of the main regulatory pathways.The animal experiment results showed that at 72 hours after modeling,compared with the model group,the neurological function score,brain tissue water content,and blood-brain barrier permeability index evans blue(EB)content of the Angong Niuhuang pill group were significantly decreased[neurological function score:1.62±0.62 vs.2.23±0.58,brain water content:(77.7±0.49)%vs.(79.9±0.04)%,EB content(μg/L):490.50±100.79 vs.1 966.20±94.81,all P<0.05];the pathological observation of brain tissue showed that Angong Niuhuang pill could reduce the pathological damage of brain tissue around the hematoma,repair the blood-brain barrier,and alleviate brain edema;the Western blotting results showed that Angong Niuhuang pill could inhibit the protein expression of TNF-α,TNFR1,and NF-κB p65 in brain tissue[NF-κB p65 protein expresion(NF-κB p65/β-actin):2.27±0.52 vs.5.40±0.26;TNFR1 protein expression(TNFR1/β-actin):1.49±0.33 vs.2.52±0.04,TNF-α protein expression(TNF-α/β-actin):1.40±0.13 vs.2.29±0.18,all P<0.05],promote the protein expression of IκB-α(IκB-α/β-actin):0.78±0.02 vs.0.32±0.00,P<0.05).Conclusion Angong Niuhuang pill may regulate the TNF-α/NF-κB signaling pathway by inhibiting the expression of TNFR1 and promoting the expression of IκB-α,exerting neuroprotective effects.

Objective: To analyze the trends in mortality of liver cancer in Wenzhou City, Zhejiang Province from 2014 to 2022, so as to provide the evidence for improving liver cancer control measures. Methods: Data of liver cancer mortality in Wenzhou City from 2014 to 2022 were collected from Wenzhou Chronic Disease Monitoring Information System. The crude mortality were estimated and standardized by the national population census data in China in 2010, and the trends in mortality of liver cancer were analyzed with average annual percent change (AAPC). Results: There were 22 033 liver cancer deaths from 2014 to 2022, accounting for 18.08% of malignant tumor deaths and ranking the second in malignant tumor deaths. The crude mortality of liver cancer was 30.00/105 and the standardized mortality was 24.32/105, both showing decreasing trends (AAPC=-2.812% and -5.742%, both P<0.05). The standardized mortality of liver cancer were higher in men than in women (36.66/105 vs. 11.21/105, P<0.05), both showing decreasing trends (AAPC=-5.702% and -5.521%, both P<0.05). The crude mortality of liver cancer appeared a tendency towards a rise with age (P<0.05), with the highest crude mortality in the group aged 80 to 84 years, reaching 145.12/105. The crude mortality of liver cancer showed a tendency towards a decline among residents aged under 15 years, 15 to 44 years, 45 to 64 years and 65 years and above (AAPC=-20.311%, -6.569%, -7.408% and -3.177%, all P<0.05). Conclusions The mortality of liver cancer showed a tendency towards a decline in Wenzhou City from 2014 to 2022. Men and the elderly were high-risk groups for liver cancer deaths, and prevention should be strengthened based on risk factors.

Objective: To investigate the mortality and life loss of female breast cancer in Wenzhou City, Zhejiang Province from 2014 to 2022, so as to provide the evidence for prevention and control of breast cancer. Methods: Data of female breast cancer deaths in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management information System from 2014 to 2012. The mortality of breast cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010 (Chinese-standardized rate) and the world standard population first introduced by Segi (world-standardized rate). The life loss were measured using potential years of life lost (PYLL), rate of potential years of life lost (PYLLR) and average years of life lost (AYLL). The trends in mortality, PYLLR and AYLL were analyzed using the average annual percent change (AAPC). Results: Totally 2 523 deaths were reported due to breast cancer from 2014 to 2022, ranking fifth in the order of female malignant tumor deaths. The crude mortality of female breast cancer was 7.13/105, showing an increasing trend with AAPC of 2.186% (P<0.05). The Chinese population-standardized mortality and global population-standardized mortality were 5.93/105 and 4.39/105, showing no significant trend with AAPC of -0.617% and -0.602% (both P>0.05), respectively. The crude mortality of female breast cancer appeared a tendency towards a rise with age (P<0.05). The crude mortality of breast cancer in females aged 65 years and older showed an increasing trend (AAPC=3.283%, P<0.05), but there were no significant tendency aged 15 to <45 years and 45 to <65 years (AAPC=-1.011% and -1.850%, both P>0.05). The PYLL, PYLLR and AYLL of breast cancer were 41 227.50 person-years, 1.23‰ and 19.44 years per person, respectively. AYLL showed a decreasing trend (AAPC=-1.969%, P<0.05), and PYLLR showed no significant trend (AAPC=-0.527%, P>0.05). Conclusions The mortality of female breast cancer in Wenzhou City appeared a tendency towards a rise from 2014 to 2022, and AYLL appeared a downward trend. Females aged 65 years and older were the key groups for the prevention and control of breast cancer.

The codon sequence of the S1 protein of the SARS-CoV-2 Beta variant was optimized ac-cording to the preference of CHO cells and cloned into pSN expression vector to construct the re-combinant plasmid pSN-Beta-sl.Recombinant protein was expressed in CHO cells,identified using SDS-PAGE and Western blot,and purified through affinity chromatography.BALB/c mice were immunized with purified recombinant protein Beta-S1 combined with aluminum hydroxide adju-vant.Specific IgG antibody and its subtypes in serum and the cross-neutralization antibody activity against SARS-CoV-2 variants were evaluated.The results showed that the recombinant plasmid pSN-Beta-S1 was successfully constructed,and the recombinant protein Beta-S1 was produced u-sing the CHO cell expression system.The purified recombinant protein had a single band of about 120 kDa with the purity exceeding 85％and can bind to RBD pAb and strep-tag mAb.The recom-binant S1 protein showed good immunogenicity in BALB/c mice.The titers of specific IgG antibodies against RBD protein and S1 protein reached 1∶66 260 and 1∶133 120 on average 21 d after the third immunization,the antibody subtypes were mainly inclined to IgG1.Serum neutrali-zing antibody titer was 1∶629 for wild type,1∶1 720 for Beta,1∶374 for Delta,1∶77 for Omi-cron BA1 and 1∶101 for Omicron BA2.In this study,S1 recombinant protein of SARS-CoV-2 Beta variant was successfully expressed in CHO cell expression system and produced good immunoge-nicity and cross-neutralizing activity in BALB/c mice.These results provide a reference for the fur-ther development of broad-spectrum SARS-CoV-2 vaccine.

Objective:To assess the relationship between smoking status and sleep duration in male adults in urban-rural areas of 15 provinces (municipalities, autonomous regions) in China in 2015.Methods:Data were derived from the China Nutritional Transition Cohort Study 2015, a total of 4 419 participants aged 18-64 years, including 1 713 urban males (38.8%) and 2 706 rural males (61.2%), with complete information about smoking status and sleep duration were included in the final analysis. Based on the number of cigarettes consumed daily, the current smokers were classified to be heavy (25 cigarettes/d and above), moderate (15-24 cigarettes/d), and light (1-14 cigarettes/d). Sleep duration was classified to be insufficient (<7 h/d), sufficient (7-9 h/d), and excessive (9 h/d and above). Two-level mixed-effects linear and logistic regression models were used for association analysis.Results:The smoking rates in male adults in urban and rural areas were 45.7% and 53.8%, respectively. In male heavy smokers in urban and rural areas, the proportions of sufficient sleep were the lowest (66.7% and 68.1%). However, the proportions of sleep deprivation were highest (15.3% and 20.3%). After controlling for confounding factors, the net effect on male heavy smokers was a significant decrease of 0.21 h/d ( β=-0.21, 95% CI: -0.44 - -0.01) in sleep duration. Moreover, the odds ratio for insufficient sleep were 1.83 (95% CI: 1.03-3.23) in male heavy smokers in rural area compared with nonsmokers. Conclusion:Heavy smoking is associated with decreased sleep duration and increased risk of sleep deprivation in male adults in rural China.

Objective:To investigate longitudinal association between smoking behavior and obesity risk in male adults in China from 1991 to 2015.Methods:A total of 32 169 male adults aged 18-64 years who participated in two or more rounds of China Health and Nutrition Survey (CHNS, 1991-2015) and had complete information of demographic characteristics, smoking status and physical measurements were selected as the study subjects. According to whether the subjects smoked or not and the number of cigarettes smoked per day, the subjects were divided into four groups: nonsmoker, light smoker (1-14 cigarettes/d), moderate smoker (15-24 cigarettes/d) and heavy smoker (≥25 cigarettes/d). The distribution of body mass index (BMI), waist circumference (WC), general obesity and central obesity of subjects with different smoking status were observed. Two-level mixed effect linear regression model and logistic regression model were used to analyze the relationship between smoking status and obesity risk.Results:Compared with nonsmokers, the BMI decreased by 0.19 kg/m 2 in light smokers (95% CI:-0.27--0.10), 0.40 kg/m 2 in moderate smokers (95% CI:-0.49--0.31), and 0.36 kg/m 2 in heavy smokers (95% CI:-0.53--0.19), respectively, and the WC decreased by 0.49 cm in light smokers (95% CI:-0.76--0.21), 0.80 cm in moderate smokers (95% CI:-1.08--0.51) and 0.79 cm in heavy smokers (95% CI:-1.38--0.36) in, respectively. Compared with nonsmokers, the odds ratio of the risk for general and abdominal obesity were 0.70 (95% CI:0.62-0.79) and 0.78 (95% CI:0.73-0.84) in light smokers, 0.61 (95% CI:0.55-0.69) and 0.74 (95% CI:0.70-0.79) in moderate smokers and 0.78 (95% CI:0.65-0.96) and 0.84 (95% CI:0.76-0.95) in heavy smokers, respectively. Conclusions:From 1991 to 2015, the BMI, WC, prevalence of general and abdominal obesity in male adults showed a significant upward trends in both nonsmokers and smokers (light, moderate and heavy) in China, suggesting that smoking is negatively associated with the risk for obesity in male adults.

Objective To study the effect of baseline clinical characteristics of elderly female patients on their long-term ischemic cardiovascular events.Methods Of the 614elderly patients admitted to our center from April 2008to July 2010,144elderly female patients were divided into female cardiovascular events group(n=43)and female control group(n=101),470elderly male patients were divided into male cardiovascular events group(n=127)and male control group(n= 343).Their baseline clinical characteristics were compared.The patients were followed up for 4.5-6.7(5.6±0.9)years,during which the relationship between first ever acute ischemic cardiovascular events and their clinical factors were analyzed.Results The incidence of grade 2hypertension,grade 3hypertension and hypercholesterolemia,the ratios of antiplatelet drug therapy,CCB therapy and hypoglycemic drug therapy were significantly higher while the history of smoking was significantly shorter,the incidence of chronic renal insufficiency and the ratios of statins therapy,nitrates therapy and ACEI/ARB therapy were significantly lower in female patients than in male patients.The incidence of chronic renal insufficiency was significantly higher in female cardiovascular events group than in female control group(9.3％vs 1.0％,P=0.03).The age was significantly older,the incidence of CHD,ischemic cerebral stroke,chronic obstructive pulmonary disease and the ratio of nitrates therapy were significantly higher in male cardiovascular events group than in male control group.Cox multivariate regression analysis showed that the endpoint events were related with CHD,grade 2hypertension,grade 3hypertension,hypercholesterolemia,chronic renal insufficiency in female patients(HR=2.56,95％CI:1.19-5.54,P=0.017;HR=3.29,95％ CI:1.14-9.52,P=0.028;HR=2.77,95％CI:1.08-7.12,P=0.034;HR=2.61,95％CI:1.27-5.36,P=0.009;HR=22.70,95％CI:5.22-98.78,P=0.000)and were related with age,CHD and ischemic cerebral stroke in male patients(P＜0.05,P＜0.01).Conclusion The effect of baseline clinical characteristics of elderly patients on their long-term ischemic cardiovascular events is different in males and females.The incidence of long-term cardiovascular events is closely related with the risk factors for cardiovascular disease in elderly females.