OBJECTIVE To investigate the mechanism of gossypol acetic acid （GAA） in the treatment of uterine fibroids. METHODS Human leiomyoma cells SK-UT-1 were selected as objects to investigate the effects of different concentrations （5， 10， 20， 40， 80， 160 μmol/L） of GAA on the activities of cell proliferation. 4D-DIA proteomic detection and bioinformatics analysis were carried out to screen differential proteins. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway analysis were performed. The expressions of top 3 proteins [N-myc downstream regulated gene 1 （NDRG1）， epidermal growth factor receptor feedback inhibitor 1 （ERRFI1）， CXC chemokine ligand 3 （CXCL3）] with differential fold changes in SK-UT-1 cells were determined. RESULTS 10-160 μmol/L GAA could significantly reduce the survival rate of SK- UT-1 cells （P＜0.05）. Proteomics results showed that a total of 921 differentially expressed proteins were obtained， including 254 up-regulated proteins and 667 down-regulated proteins. The differentially expressed proteins were mainly distributed in mitochondria， nucleus， extracellular matrix， etc. Bioinformatics results showed that differentially expressed proteins were mainly involved in signaling pathways such as PI3K/AKT （phosphoinositide 3-kinase/protein kinase B）， MAPK （mitogen-activated protein kinase）， TNF （tumor necrosis factor）， etc.， which mainly involved cell apoptosis， aging， and movement. GAA significantly decreased protein expressions of NDRG1 and CXCL3 （P＜0.05）， but increased protein expression of ERRFI1 （P＜0.05）. CONCLUSIONS The improvement effect of GAA on uterine fibroids may involve signaling pathways such as PI3K/AKT， MAPK， TNF， etc. It can improve the occurrence and development of uterine fibroids by downregulating the expressions of NDRG1 and CXCL3 proteins， upregulating the expression of ERRFI1 protein， and affecting the proliferation and apoptosis of uterine fibroid cells.

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Objective To observe the effects of amyloid-β(Aβ)receptor PirB on mouse astrocyte proliferation and reactive astrogliosis in vitro.Methods Mouse primary astrocytes were cultured,and divided into control group,Aβ group,Aβ+0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group,Aβ+Fluspirilene group,Aβ+GFP-LV group,and Aβ+mPirB-LV group.The mouse astrocytes were treated with soluble PirB extracellular peptide PEP or PirB inhibitor Fluspirilene,respectively,to inhibit endogenous PirB receptor,or overexpressed PirB gene via lentivirus transfection and then treated with Aβ1-42 oligomers.The proliferation of astrocytes was observed by RTCA and EdU methods,and the mRNA expression levels of S-100 calcium-binding protein B(S-100β),Vimentin,Nestin and amyloid precursor protein(APP)associated with reactive astrogliosis of astrocytes were observed by real-time PCR,and the expression level of glial fibrillary acid protein(GFAP)was detected by Western-blotting.Results The results of RTCA monitoring showed that normalized cell index(NCI)values of each group decreased sharply after treatment,and then increased gradually and tended to be stable.The results of EdU staining showed that the proliferative activity of astrocytes was significantly enhanced in the Aβ group(P<0.05)compared with control group;Compared with Aβ group,cell proliferation activity in Aβ + 0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group and Aβ+Fluspirilene group were significantly decreased(P<0.01 or P<0.001).The results of real-time PCR showed that compared with control group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ group were significantly increased(P<0.05);Compared with Aβ group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ+0.4 μmol/L PEP group were significantly decreased(P<0.01);Compared with Aβ+GFP-LV group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ +mPirB-LV group were significantly increased(P<0.05).The results of Western blotting showed that compared with control group,the expression of GFAP in Aβ group was significantly increased(P<0.05);Compared with Aβ group,the expression of GFAP in Aβ+0.4 μmol/L PEP group was significantly decreased(P<0.05).Conclusions PirB is an upstream molecule which could regulate astrocyte proliferation and reactive astrogliosis,and inhibiting PirB receptor in astrocytes may be a potential treatment for Alzheimer's disease.

Objective:To evaluate the associations of sociodemographic characteristics and lifestyle factors with longevity status in older adults in China.Methods:After excluding those born after 31 st December 1938, a total of 51 870 older adults from the China Kadoorie Biobank (CKB) were included. The attained age was defined according to the survival age or age on 31 st December 2018. According to the attained age, the old persons were categorized into non-longevity (died before age 80 years) and longevity (attained age ≥80 years). The longevity group was further divided into two groups: longevity with death occurring before 2019, and longevity and survival to 2019. The information about socio-demographic characteristics and lifestyles was collected at the 2004-2008 baseline survey. Multinomial logistic regression models were used to analyze the associations between exposure factors and outcomes by taking the non-longevity group as the reference group. Results:A total of 51 870 older adults aged 65-79 years in the baseline survey were included for analysis. During a follow-up for (10.2±3.5) years, 38 841 participants were longevity, and 30 354 participants still survived at the end of 2018. Compared to men, rural populations, non-married individuals, those with an annual household income of less than 10 000 yuan, and those with education levels of primary school or below, the adjusted ORs(95% CI) for longevity and survival to 2019 in women, urban residents, married individuals, those with annual household incomes ≥20 000 yuan, and those with education levels of college or university were 1.68 (1.58-1.78), 1.69 (1.61-1.78), 1.15 (1.10-1.21), 1.44 (1.36-1.53), and 1.32 (1.19-1.48), respectively. The OR (95% CI) for longevity and survival to 2019 was 1.09 (1.08-1.10) for those with an increase of 4 MET-hour/day in total physical activity level. With those who never or almost never smoked, had no alcohol drinking every week, had normal weight (BMI: 18.5-23.9 kg/m 2), and WC <85 cm (man)/<80 cm (woman) as the reference groups, the ORs(95% CI) of longevity and survival to 2019 were 0.64 (0.60-0.69) for those smoking ≥20 cigarettes per day, 1.29 (1.14-1.46) for those with alcohol drinking every week, 1.13 (1.01-1.26) for those with pure alcohol drinking <30 g per day, 0.56 (0.52-0.61) for those being underweight, 1.27 (1.19-1.36) for those being overweight, 1.23 (1.11-1.36) for those with obesity, and 0.86 (0.79-0.93) for those with central obesity. Further stratified analysis by WC was performed. In the older adults with WC <85 cm (man)/<80 cm (woman), the ORs (95% CI) of longevity and survival was 1.80 (1.69-1.92) for those with each 5 kg/m 2 increase in BMI and 1.02 (0.96-1.08) for those with WC ≥85 cm (man)/≥80 cm (woman). There was a statistically significant difference in the association between BMI and longevity between the two WC groups (interaction test P<0.001). Conclusion:This study showed that women, the married, those with higher socioeconomic status and education level, and those with healthy lifestyles were more likely to achieve longevity.

Objective:To research the association between exposure to solid fuels for heating and its duration and the risk of respiratory diseases morbidity.Methods:Data from the China Kadoorie Biobank project sited in Pengzhou City, Sichuan Province. Cox proportional hazard regression model was used to analyze the association between exposure to solid fuels for heating and its duration and the risk of total respiratory diseases and the association between exposure to solid fuels for heating and the risk of chronic obstructive pulmonary disease (COPD) and pneumonia among respiratory diseases.Results:A total of 46 082 participants aged 30-79 years were enrolled, with 11 634 (25.25%) heating during the winter, of whom 8 885 (19.28%) used clean fuels and 2 749 (5.97%) used solid fuels, of whom 34 448 (74.75%) did not heat. After controlling for multiple confounding factors, Cox proportional hazard regression model was used, which revealed that compared with clean fuels, unheating could reduce the risk of total respiratory disease ( HR=0.81,95% CI:0.77-0.86), COPD ( HR=0.86,95% CI:0.78-0.95) and pneumonia ( HR=0.80,95% CI:0.74-0.86), respectively. Exposure to solid fuels increased the risk of total respiratory disease ( HR=1.10, 95% CI:1.01-1.20) and were not associated with COPD and pneumonia. Compared with no solid fuel exposure, the risk of total respiratory disease (1-19 years: HR=1.23, 95% CI:1.10-1.37; 20-39 years: HR=1.25, 95% CI:1.16-1.35; ≥40 years: HR=1.26, 95% CI:1.15-1.39) and COPD (1-19 years: HR=1.21, 95% CI:1.03-1.42; 20-39 years: HR=1.30, 95% CI:1.16-1.46; ≥40 years: HR=1.35, 95% CI:1.18-1.54) increased with the length of exposure of solid fuels (trend test P<0.001). Solid fuels exposure for 1-19 years and 20-39 years increased the risk of COPD by 23% ( HR=1.23,95% CI:1.02-1.49) and 16% ( HR=1.16, 95% CI:1.00-1.35). Conclusion:Heating solid fuels exposure increases the risk of total respiratory disease, COPD, and pneumonia.

Objective:To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors.Methods:This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels.Results:Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M ( Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) ( OR=1.23, 95% CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced ( OR=0.68, 95% CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95% CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95% CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95% CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95% CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions:Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

Objective:To investigate the morbidity of cerebrovascular disease among residents ≥30 years in Pengzhou, Sichuan Province, and analyze the effect of physical activity level on the risk of morbidity of cerebrovascular disease.Methods:From 2004 to 2008, people from Pengzhou, Sichuan Province were randomly selected. All the local people aged 30-79 were asked to receive a questionnaire survey, physical examination, and long-term follow-up to determine the morbidity of cerebrovascular disease. The physical activity level and the morbidity of cerebrovascular disease were described, and Cox proportional hazard regression models were used to evaluate the association of domain-specific physical activity with the risk of morbidity of cerebrovascular disease.Results:In 55 126 participants, there were 5 290 new cases of cerebrovascular disease, with a cumulative incidence of 9.60%. After the adjustment for multiple confounding factors, multivariate Cox proportional hazard regression analysis showed that increased levels of occupational, transportation, and total physical activity reduced the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). The highest group of occupational physical activity level had the lowest risk of cerebrovascular disease, with a hazard ratio ( HR) value of 0.81 (95% CI: 0.75-0.88), the highest group of transportation physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.84 (95% CI: 0.78-0.91), the highest group of total physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.87 (95% CI: 0.80-0.94), compared with the lowest group of corresponding physical activity. No association was found between the household/leisure-time physical activity level and the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Conclusions:In project areas of Pengzhou, Sichuan Province, increased physical activity has been associated with reduced morbidity of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Increased levels of physical activity in adults are encouraged for health benefits.

Objective:To examine the associations of BMI and waist circumference (WC) with the risk of chronic kidney disease (CKD) and its subtypes in adults in China.Methods:The data from the China Kadoorie Biobank were used. After excluding those with cancer, coronary heart disease, stroke, or CKD at baseline survey, 480 430 participants were included in this study. Their body height and weight, and WC were measured at baseline survey. Total CKD was defined as diabetic kidney disease (DKD), hypertensive nephropathy (HTN), glomerulonephritis (GN), chronic tubulointerstitial nephritis (CTIN), obstructive nephropathy (ON), CKD due to other causes, and chronic kidney failure. Cox proportional hazards regression model was used to estimate the associations between exposure factors and risks of outcomes.Results:During a follow-up period of (11.8±2.2) years, 5 486 cases of total CKD were identified, including 1 147 cases of DKD, 340 cases of HTN, 1 458 cases of GN, 460 cases of CTIN, 598 cases of ON, 418 cases of CKD due to other causes, and 1 065 cases of chronic kidney failure. After adjusting for socio-demographic factors, lifestyle factors, baseline prevalence of hypertension and diabetes, and WC and compared to participants with normal BMI (18.5-23.9 kg/m 2), the hazard ratios ( HRs) of total CKD for underweight (<18.5 kg/m 2), overweight (24.0-27.9 kg/m 2), and obese (≥28.0 kg/m 2) were 1.42 (95% CI: 1.23-1.63), 1.00 (95% CI: 0.93-1.08) and 0.98 (95% CI: 0.87-1.10), respectively. Stratification analysis by WC showed that BMI was negatively associated with risk for total CKD in non-central obese participants (WC: <85.0 cm in men and <80.0 cm in women) ( HR=0.97, 95% CI: 0.96-0.99), while the association was positive in central obese participants (≥90.0 cm in men and ≥85.0 cm in women) ( HR=1.03, 95% CI: 1.01-1.05). The association between BMI and GN was similar to that of total CKD. BMI was associated with an increased risk for HTN, with a HR of 1.12 (95% CI: 1.06-1.18) per 1.0 kg/m 2 higher BMI. After adjusting for potential confounders and BMI, compared to participants with non-central obesity, the HRs for pre-central obesity (WC: 85.0-89.9 cm in men and 80.0-84.9 in women) and central obesity were 1.26 (95% CI: 1.16-1.36) and 1.32 (95% CI: 1.20-1.45), respectively. With the exception of HTN and CTIN, WC was positively associated with risks for all CKD subtypes. Conclusions:BMI-defined underweight and central obesity were independent risk factors for total CKD, and BMI and WC had different associations with risks for disease subtypes.

Objective:To investigate the association between solid fuel use for heating, smoking, and respiratory diseases.Methods:This study is based on the Qingdao project of the China Kadoorie Biobank. After screening, 26 165 individuals were included in the study. We employed Cox proportional hazards regression models, stratified by risk age (in 5-year intervals) and sex while adjusting for confounding variables such as occupation and physical activity level to analyze the association between solid fuel use for heating, smoking, and increased risk of respiratory diseases.Results:Among the 26 165 participants, the average age of those using solid fuel for heating was (52.57±10.31) years, with females constituting 58.04% and former/current smokers accounting for 65.38%. The results indicated that both the solid fuel group and the former/current smoking group had a higher risk of respiratory diseases, with hazard ratios ( HR) (95% CI) of 1.21 (1.04-1.41) and 1.41 (1.16-1.71), respectively. For the duration of solid fuel use, the HR (95% CI) for 20 years or more, it was 1.27 (1.07-1.51). The multiplicative interaction term between solid fuel use and smoking was statistically significant. Conclusions:The use of solid fuel for heating and smoking significantly increases the risk of respiratory diseases, and there may be a multiplicative interaction between solid fuel use and smoking.

Objective To investigate the epidemiological characteristics and spatial distribution characteristics of Clonorchis sinensis human infections in Guangdong Province from 2016 to 2022, so as to provide insights into formulation of the clonorchiasis control measures in the province. Methods Xinhui District of Jiangmen City, Longmen County of Huizhou City and Wengyuan County of Shaoguan City in Guangdong Province were selected as fixed surveillance sites for human clonorchiasis from 2016 to 2022, and additional 10% to 15% counties (districts) endemic for clonorchiasis were sampled from Guangdong Province as mobile surveillance sites each year from 2016 to 2022. A village (community) was randomly selected from each surveillance site according to the geographical orientations of east, west, south, north and middle, and subjects were randomly sampled from each village (community). C. sinensis eggs were detected in subjects’ stool samples using the Kato-Katz technique, and the prevalence and intensity of C. sinensis infections were calculated. In addition, subjects’ gender, age, ethnicity, educational level and occupation were collected. The Guangdong Provincial 1:1 million electronic map in vector format was downloaded from the National Geomatics Center of China, and kernel density analysis and spatial autocorrelation analysis of C. sinensis human infections in Guangdong Province from 2016 to 2022 were performed using the software ArcGIS 10.7. Results A total of 153 188 residents were tested for C. sinensis infections in Guangdong Province from 2016 to 2022, including 75 596 men (49.35%) and 77 592 women (50.65%), and there were 5 369 residents infected with C. sinensis, with 3.50% overall prevalence of infections. The prevalence rates of severe, moderate and mild C. sinensis infections were 0.76%, 7.26% and 91.97% among C. sinensis-infected residents in Guangdong Province from 2016 to 2022, and there were age-, gender-, ethnicity-, occupation- and educational level-specific prevalence of C. sinensis human infections (χ² = 2 578.31, 637.33, 52.22, 2 893.28 and 1 139.33, all P values < 0.05). Global spatial autocorrelation analysis showed a cluster in the prevalence of C. sinensis human infections in Guangdong Province (Moran’s I = 0.63, Z = 27.31, P < 0.05). Kernel density analysis showed that the prevalence of C. sinensis human infections with a high kernel density in Guangdong Province was mainly distributed along the Zhujiang River basin in Pearl River Delta areas, followed by in eastern and northern Guangdong Province. In addition, local spatial autocorrelation analysis identified 73 high-high clusters of the prevalence of C. sinensis human infections in Guangdong Province. Conclusions The prevalence of C. sinensis human infections was high in Guangdong Province from 2016 to 2022, and mild infection was predominant among all clonorchiasis cases, with spatial clusters identified in the prevalence of C. sinensis human infections. Targeted clonorchiasis control measures are required among high-risk populations and areas.