AIM: To investigate the effects of insulin-like growth factor 1(IGF-1)on the secretion of transforming growth factor β2(TGF-β2), matrix metalloproteinase 2(MMP-2)and hypoxia-inducible factor 1α(HIF-1α)in human scleral fibroblasts(HSF)and their mechanism.METHODS: The cells were cultured with IGF-1 and PI3K/AKT pathway inhibitor LY294002, respectively. CCK-8 method was used to detect cell viability and determine the optimal concentration and time of drug action. Cell migration activity was observed by cell scratch method. To determine the effects of IGF-1 on HSF cells and the regulatory role of PI3K/AKT pathway, HSF cells were divided into control group(without drugs), IGF-1(80 μg/L)group, IGF-1+LY294002(80 μg/L+5 mmol/L)group, and LY294002(5 mmol/L)group, and were cultured for 24 h; the protein expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT were detected by Western blot; the fluorescence expression of TGF-β2, MMP-2 and HIF-1α was detected by cellular immunofluorescence.RESULTS: The results of CCK-8 showed that the cell viability of the 80 μg/L IGF-1 group cultured with different concentrations of IGF-1 was the highest(all P<0.05), and the cell viability of the 80 μg/L IGF-1 group at 24 h was the highest under different culture times. Therefore, the concentration of IGF-1 was selected as 80 μg/L for 24 h. The viability of cells cultured with different concentrations of LY294002 gradually decreased from 6 h(all P<0.05). According to the IC50 value, therefore, the concentration of LY294002 was selected as 5 mmol/L for 24 h. The cell scratch results showed that compared with the control group, the cell mobility of 40 μg/L and 80 μg/L IGF-1 groups was increased(all P<0.05). Compared with the control group, cell mobility in the 2.5 and 5 mmol/L LY294002 groups was decreased(all P<0.05). Western blot results showed that compared with the control group, the protein expressions of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1+LY294002 group were decreased(all P<0.05). The results of cell immunofluorescence showed that compared with the control group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1+LY294002 group were significantly decreased(all P<0.05).CONCLUSION: IGF-1 promoted the proliferation and migration of human HSF. IGF-1 may up-regulate the expression of TGF-β2, MMP-2 and HIF-1α in HSF through the PI3K/AKT signaling pathway, and participate in the occurrence and development of myopia.

Objective:To study the association between subtypes of hypertension and risk for all-cause mortality and cardio-cerebrovascular mortalities in the elderly in communities of Beijing.Methods:The data were collected from the Beijing Healthy Aging Cohort Study. The elderly in 5 urban areas (former Xicheng, former Xuanwu, Fangshan, Haidian and Tongzhou) and 4 rural areas (Yanqing, Miyun, Huairou and Daxing) in Beijing were selected as the study subjects by multi-stage stratified cluster random sampling. The baseline survey was conducted from July 2009 to September 2015. The follow-up was conducted until March 31, 2021, and a total of 6 326 participants were enrolled. Cox proportional hazard regression model was used to analyze the association of SBP, DBP, normal blood pressure, high normal blood pressure, simple systolic hypertension, simple diastolic hypertension and systolic diastolic hypertension with all-cause mortality and cardio-cerebrovascular mortality.Results:By March 31, 2021, the median follow-up time was 6.30 years, the all-cause mortality density was 201.67/10 000 person-years, and the cardio-cerebrovascular mortality density was 90.20/10 000 person-years. Multivariate Cox proportional hazard regression model analysis showed that the risk for all-cause mortality increased by 5.6% ( HR=1.056, 95% CI: 1.020-1.092), and the risk for cardio-cerebrovasculvar mortality increased by 12.5% ( HR=1.125, 95% CI: 1.071-1.182) for every 10 mmHg increase in SBP. The risk for all-cause mortality increased by 8.6% ( HR=1.086, 95% CI: 1.023-1.152), and the risk for cardio-cerebrovascular mortality increased by 19.9% ( HR=1.199, 95% CI: 1.101-1.306) for every 10 mmHg increase in DBP. Compared with the normal blood pressure group, the risk for all-cause mortality increased by 64.8% ( HR=1.648, 95% CI: 1.049-2.591) and the risk for cardio- cerebrovascular mortality increased by 112.8% ( HR=2.128, 95% CI: 1.069-4.233) in the simple diastolic hypertension group. The risk for all-cause mortality increased by 34.4% ( HR=1.344, 95% CI: 1.023-1.467) and the risk for cardio-cerebrovascular mortality increased by 111.3% ( HR=2.113, 95% CI: 1.384-3.225) in the systolic-diastolic hypertension group. Conclusions:In the elderly in communities of Beijing, beside systolic-diastolic hypertension. It is necessary to pay close attention to the simple diastolic hypertension, which has lower prevalence, and give targeted prevention and treatment.

Objective:To investigate the association of urinary albumin-to-creatinine ratio (UACR) in normal range and cardiovascular health (CVH) score with cardio-cerebroascular and all-cause mortality in urban elderly residents in Beijing.Methods:Based on Beijing Healthy Aging Cohort Study, data from 1 817 elderly participants with normal UACR were analyzed, and UACR was used as both continuous and categorical variable. "Life's Essential 8" was used to develop a CVH score. Statistical analysis was performed by using software SPSS 26.0 and R 4.2.1, including two independent samples t-test, χ2 test and non-parametric test. Multivariable Cox proportional hazard regression models stratified by CVH score and the restricted cubic spline were used to analyse the association of UACR with the risk for cardio-cerebrovascular and all-cause mortality. Results:By March 31, 2021, the median follow-up time M ( Q1, Q3) was 11.28 (10.84, 11.36) years, a total of 308 deaths were recorded during follow-up, and the mortality density was 163.87/10 000 person-years. The age of the participants was (71.4±6.6) years, and 1 070 participants were women. The results showed that the risk for both cardio-cerebrovascular disease and all-cause mortality decreased with the decrease of UACR in the low CVH score group ( HR=0.500, 95% CI: 0.341-0.734; HR=0.793, 95% CI: 0.647-0.971), and in the high CVH score group, there was a decreasing trend in the risk for cardio-cerebrovascular mortality with the decrease of UACR ( HR=0.665, 95% CI: 0.447-0.990). Compared with the participants with low CVH score and higher UACR, the risk for cardio-cerebrovascular and all-cause mortality decreased by 68.9% and 45.6%, respectively, in the participants with high CVH score and lower UACR ( HR=0.311, 95% CI: 0.131-0.739; HR=0.544, 95% CI: 0.360-0.822), and the risk for all-cause mortality decreased by 26.7% in the participants with high CVH score and higher UACR ( HR=0.733, 95% CI: 0.542-0.993). Conclusions:In urban elderly residents in Beijing, higher UACR were associated with a significantly increased risk for cardio-cerebrovascular and all-cause mortality, and in the low-CVH score group, decreased UACR was protective factor against cardio-cerebrovascular and all-cause mortality. The combined effect of cardiovascular health status and normal UACR had a greater protection against the risk for cardio-cerebrovascular and all-cause mortality.

Objective:To describe and analyze the distribution characteristics of a body shape index (ABSI) and its association with all-cause mortality in the elderly in communities of Beijing.Methods:The baseline and follow-up data of 10 423 subjects in Beijing Healthy Aging Cohort Study were used. The endpoint outcome was all-cause mortality in follow-up. The associations of ABSI, BMI and waist circumference with all-cause mortality were analyzed with a Cox proportional hazard regression model.Results:The mean follow-up time in this cohort was 6.36 years and the all-cause mortality was 15.27%. The restricted cubic spline results showed that ABSI showed a "U" association with all-cause mortality in the total population. After adjustment for confounding factors, compared with the normal ABSI group, the risk for all-cause mortality was higher in the low ABSI group ( HR=1.69, 95% CI: 1.32-2.17) and high ABSI group ( HR=1.75, 95% CI: 1.40-2.18). Compared with the normal BMI group, low BMI was associated with an increased risk for all-cause mortality ( HR=1.70, 95% CI: 1.40-2.08). Compared with the normal waist circumference group, central obesity was associated with a decreased risk for all-cause mortality ( HR=0.89, 95% CI: 0.80-0.99). The results of gender specific analysis on ABSI association with all-cause mortality were similar to that in total population, but the strength of association varied among different age groups. Cross-grouping results showed that older people with normal BMI and waist circumference and abnormal ABSI had an increased risk of all-cause mortality ( HR=1.91, 95% CI: 1.22-2.99). Conclusions:In Beijing, ABSI is correlated with the risk for all-cause mortality in the elderly population, which is more sensitive and specific than the traditional indicators (BMI and waist circumference). They can be used as one of the physical measurement indicators for all-cause mortality risk prediction in the health risk assessment and management in the elderly.

Objective:To explore the association between physical activity (PA) level and all-cause mortality in the elderly with different obesity status in Beijing.Methods:The study subjects were from the Cardiovascular and Cognitive Healthy Study in Middle-Aged and Elderly Residents of Beijing, a total of 3 746 individuals aged ≥60 years in the baseline survey between 2013 and 2015 were included in the study. Questionnaire survey and physical examination were conducted to collect the basic information of the individuals. The metabolic equivalent of the elderly was used to calculate the PA level, and an international PA questionnaire was used to determine the PA intensity. BMI, waist-to-height ratio (WHtR) and a body shape index (ABSI) were used to evaluate individuals' obesity status. The distribution of different PA levels under different obesity states was described by using bar chart and cumulative percentage bar chart. Cox proportional hazard regression model was used to analyze the correlation between the level of PA and all-cause mortality risk in different types of obesity status.Results:By December 31, 2019, the median follow-up time was 5.46 years, and the mortality density was 244.55/10 000 person-years. Compared with the individuals in high-PA intensity group, the all-cause mortality risk increased by 41% ( HR=1.41, 95% CI: 1.14-1.76) and 122% ( HR=2.22, 95% CI: 1.76-2.81), respectively, in moderate and low PA intensity groups. Compared with the individuals in high-PA intensity-high-obesity group, based on the BMI, the all-cause mortality risk increased by 85% ( HR=1.85, 95% CI: 1.08-3.16) and 250% ( HR=3.50, 95% CI: 2.01-6.10) in those in moderate-PA intensity-high-obesity group and in low-intensity-high-obesity group. Based on the WHtR, the all-cause mortality risk increased by 53% ( HR=1.53, 95% CI: 1.02-2.29) and 218% ( HR=3.18, 95% CI: 2.09-4.86), respectively, in those with moderate-PA intensity-high-obesity and those with low-PA intensity-high-obesity. According to the ABSI, the all-cause mortality risk increased by 120% in those in low-PA intensity-high-obesity group ( HR=2.20, 95% CI: 1.53-3.18). Based on any one of the indicators BMI, WHtR, or ABSI, there was no significant difference in all-cause mortality risk between high-intensity-moderate-obesity group and high-intensity-low-obesity group (all P>0.05). Conclusions:PA level is closely associated with the all-cause mortality risk in the elderly in communities of Beijing. Increasing PA level can not only reduce the all-cause mortality risk but also reduce even eliminate the excess all-cause mortality risk associated with obesity.

Objective:To analyze the association between different lipid indicators and cardio-cerebrovascular mortality in the elderly, identify a better lipid indicator for the risk for cardio-cerebrovascular mortality in the elderly in communities of Beijing.Methods:The elderly aged 60 years and above were selected from the Beijing Healthy Aging Cohort Study from July 2009 to September 2015. Remnant cholesterol (RC) was derived by calculation. The Cox proportional hazard regression models determined the HR and 95% CI incidating the associations of baseline different lipid indicators with cardio-cerebrovascular and all-cause mortality. Results:By March 31, 2021, with a mean follow-up duration of 6.88 years in the study population, a total of 492 cardio-cerebrovascular deaths and 1 056 all-cause deaths wre recorded. The HR values indicating the association between LDL-C, HDL-C, and RC were 0.87 (95% CI: 0.78-0.97), 0.46 (95% CI: 0.35-0.62), and 1.29 (95% CI: 1.14-1.45) for cardio-cerebrovascular mortality, respectively, and 0.93 (95% CI: 0.86-1.00), 0.66 (95% CI: 0.55-0.80) and 1.22 (95% CI: 1.12-1.33) for all-cause mortality. The associations of RC and HDL-C with cardio-cerebrovascular mortality were consistent regardless of hyperlipidemia in the elderly. Subgroup analyses showed that elevated RC was associated with increased risk for cardio-cerebrovascular mortality, and elevated HDL-C was associated with decreased risk for cardio-cerebrovascular mortality in the elderly in different gender, age, smoking status, drinking status, and diabetes status groups in communities of Beijing. Conclusion:RC might be a better potential lipid indicator for the risk for cardio-cerebrovascular mortality in the elderly in communities compared with traditional cholesterol indicator.

Hyssopus cuspidatus is an authentic medicinal herb used in Xinjiang， rich in the chemical constituents including flavonoids， phenolic acids and terpenoids. It possesses anti-inflammatory， antioxidant， and immunomodulatory effects. Modern pharmacological studies have demonstrated that H. cuspidatus exerts therapeutic effects on asthma by inhibiting airway inflammatory responses， suppressing airway remodeling， modulating the function of the hypothalamic-pituitary-adrenal axis， and relaxing bronchial smooth muscle. It also demonstrates intervention effects on chronic obstructive pulmonary disease by reducing levels of inflammatory cytokines and regulating immune balance. Additionally， H. cuspidatus can mitigate acute lung injury by inhibiting oxidative stress and intervene in lung cancer by suppressing proliferation and promoting apoptosis of lung cancer cells. In terms of clinical application， compound preparations containing H. cuspidatus， such as Hanchuan zupa granules and Luo’ou kezupa， have demonstrated favorable therapeutic effects on pulmonary diseases including asthma， cough， and pediatric bronchopneumonia. Currently， the research on precise action targets and compound matching rules of H. cuspidatus remains inadequate. Future studies should integrate modern technologies such as metabolomics to conduct in-depth exploration， thereby promoting the modernized development and clinical application of this traditional medicinal herb.

Objective To explore the association between levels of peripheral blood systemic im-mune-inflammatory indicators in early pregnancy and the risk of gestational diabetes mellitus(GDM).Methods A total of 348 pregnant women in early pregnancy who underwent regular prenatal exami-nations and established medical records were enrolled as subjects.According to whether they devel-oped GDM,the participants were divided into GDM group(n=76)and non-GDM group(n=272).General characteristics,glycemic parameters and peripheral blood systemic immune-inflammatory in-dices were compared between two groups.The predictive value of peripheral blood systemic immune-inflammatory indicators for GDM was analyzed using receiver operating characteristic(ROC)curves and binary Logistic regression analysis.Results Among 348 pregnant women in early pregnancy,76 were diagnosed with GDM,with an incidence rate of 21.84％.The gestational weight gain,hemoglobin A1c(HbA1c),fasting plasma glucose(FPG),fasting insulin(FINS)and homeostasis model assessment-insulin resistance(HOMA-IR)were significantly higher in the GDM group than those in the non-GDM group(P＜0.05).The monocyte-to-lymphocyte ratio(MLR),systemic im-mune-inflammation index(SII),systemic inflammation response index(SIRI)and C-reactive protein(CRP)levels were sig-nificantly elevated in the GDM group compared with the non-GDM group(P＜0.05).Increased levels of MLR,SII,SIRI,aggregate index of systemic inflammation(AISI)and CRP were all inde-pendent risk factors for GDM in early pregnancy(P＜0.05).The areas under the curve(AUC)of MLR,SII,SIRI,AISI and CRP levels alone and their combination for detecting the risk of GDM in the first trimester of pregnancy were 0.918,0.932,0.700,0.918,0.767 and 0.995,respective-ly.The combined detection of each index had the highest predictive value.Conclusion The ele-vated levels of MLR,SII,SIRI,AISI and CRP in peripheral blood during the first trimester of preg-nancy are associated with an increased risk of GDM,and the combined detection of the above indi-cators has higher predictive value for the occurrence of GDM.

Circular RNA(circRNA),as a kind of non-coding RNA,regulates a variety of biological functions.To explore the effect of circRNA on PEDV replication in the host porcine intestinal epi-thelial cells,this study screened and analyzed the differentially expressed circRNAs by bioinforma-tic software in African Green Monkey renal cells(Vero-E6 cells)infected by porcine epidemic di-arrhea virus(PEDV),the differentially expressed circRNA ssc_circ_PIK3C2A was identified and the secondary structure was analyzed.PCR was used to identify the ssc_circ_PIK3C2A circRNA structure,the model of PEDV-infected IPEC-J2 cells was constructed,the TCID50 test was used to validate the viral titer of PEDV.The expression of circ_PIK3C2A was detected by qRT-PCR in IPEC-J2 infected by PEDV.circ_PIK3C2A qRT-PCR was performed to detect the expression of N gene of PEDV when ssc_circ_PIK3C2A was over-expressed in IPEC-J2 cells.The results showed that ssc_circ_PIK3C2 A is a porcine circular RNA with a typical circular structure,the virus titer of PEDV reached 10-6/mL after PEDV infected IPEC-J2 cells for 48 h,the expression of circ_PIK3C2A increased extremely(P＜0.01)at 6 h after PEDV-infection,with the extension of infec-tion time,its expression gradually decreased,and the expression was the lowest at 24 h,but there was no time-dependent trend.The expression of PEDV N gene decreased significantly when ssc_circ_PIK3C2A was over-expressed in IPEC-J2 cells.In conclusion,when PEDV infects IPEC-J2 cells,the expression of porcine circ_PIK3C2A decreases,and replication of PEDV increases signifi-cantly in IPEC-J2 cells.our result provides a basis for further study of the mechanism of circular RNA on PEDV replication and its physiological activities in host cells in the future.

Objective:To study the association between subtypes of hypertension and risk for all-cause mortality and cardio-cerebrovascular mortalities in the elderly in communities of Beijing.Methods:The data were collected from the Beijing Healthy Aging Cohort Study. The elderly in 5 urban areas (former Xicheng, former Xuanwu, Fangshan, Haidian and Tongzhou) and 4 rural areas (Yanqing, Miyun, Huairou and Daxing) in Beijing were selected as the study subjects by multi-stage stratified cluster random sampling. The baseline survey was conducted from July 2009 to September 2015. The follow-up was conducted until March 31, 2021, and a total of 6 326 participants were enrolled. Cox proportional hazard regression model was used to analyze the association of SBP, DBP, normal blood pressure, high normal blood pressure, simple systolic hypertension, simple diastolic hypertension and systolic diastolic hypertension with all-cause mortality and cardio-cerebrovascular mortality.Results:By March 31, 2021, the median follow-up time was 6.30 years, the all-cause mortality density was 201.67/10 000 person-years, and the cardio-cerebrovascular mortality density was 90.20/10 000 person-years. Multivariate Cox proportional hazard regression model analysis showed that the risk for all-cause mortality increased by 5.6% ( HR=1.056, 95% CI: 1.020-1.092), and the risk for cardio-cerebrovasculvar mortality increased by 12.5% ( HR=1.125, 95% CI: 1.071-1.182) for every 10 mmHg increase in SBP. The risk for all-cause mortality increased by 8.6% ( HR=1.086, 95% CI: 1.023-1.152), and the risk for cardio-cerebrovascular mortality increased by 19.9% ( HR=1.199, 95% CI: 1.101-1.306) for every 10 mmHg increase in DBP. Compared with the normal blood pressure group, the risk for all-cause mortality increased by 64.8% ( HR=1.648, 95% CI: 1.049-2.591) and the risk for cardio- cerebrovascular mortality increased by 112.8% ( HR=2.128, 95% CI: 1.069-4.233) in the simple diastolic hypertension group. The risk for all-cause mortality increased by 34.4% ( HR=1.344, 95% CI: 1.023-1.467) and the risk for cardio-cerebrovascular mortality increased by 111.3% ( HR=2.113, 95% CI: 1.384-3.225) in the systolic-diastolic hypertension group. Conclusions:In the elderly in communities of Beijing, beside systolic-diastolic hypertension. It is necessary to pay close attention to the simple diastolic hypertension, which has lower prevalence, and give targeted prevention and treatment.