The general population cohort study in Beijing-Tianjin-Hebei area is a large-scale prospective longitudinal study conducted since 2017, which covers over 114 850 diverse populations from early life to senior age. Up to December 2021, 106 031 people had completed at least one follow-up, with an overall follow-up rate of 92.3%. Considering of the characteristics of the environmental and health problems in Beijing-Tianjin-Hebei area, in this cohort study we have focused on health problems of children and adolescents' growth and development, cardiometabolic diseases and their risk factors, aging and comorbidity, health hazards caused by air pollution. The long-term follow up of the general population cohort study in Beijing-Tianjin-Hebei area will contribute to establishing unique and invaluable data and biobank resource for scientific research. This paper aims to comprehensively describe the background, significance, current status and outcomes, limitations and challenges, and future plan and development of general population cohort study in Beijing-Tianjin-Hebei area, thus to provide reference for professionals both at home and abroad to carry out related research.

Objective:To explore the relationship of sleep quality and sleep duration with hypertension among adults aged 30-79 years old in Guangzhou.Methods:According to multi-stage stratified cluster sampling, 12 747 residents aged 30-79 years old were sampled and surveyed in Guangzhou from January 2018 to March 2019. Data on general demographic characteristics, sleep quality, sleep duration and hypertension were collected through questionnaire survey, the Pittsburgh sleep quality index (PSQI) and physical examination. Multivariate logistic regression models were used to analyze the putative association between sleep quality, sleep duration and hypertension. Restrictive cubic spline curve was used to draw the dose-response relationship curve between sleep quality, sleep time and hypertension.Results:The mean age of the subjects was (52.68±12.17) years, the prevalence of hypertension was 36.6% (4 664/12 747), the average score of PSQI was (4.70±2.88), and the average sleep time was (7.00±1.32) hours. The prevalence of hypertension was positively associated with the PSQI score. Compared to the subjects with a score less than 3, OR (95% CI) of hypertension with a PSQI score of 3-5, 5-8, ≥9 were 1.14 (1.02-1.27), 1.17 (1.03-1.34), 1.41 (1.21-1.64), respectively. The relationship between sleep duration and hypertension appeared U-shaped. Compared with 6 to 8 hours sleep duration, both sleep duration<6 hours with OR(95% CI) of 1.27(1.12-1.43) or >8 hours with OR(95% CI) of 1.20(1.05-1.38) was associated with hypertension. Conclusion:Both poor sleep quality, longer or shorter sleep duration were responsible for increased risk of cognitive impairment in older Chinese.

Objective:To explore the relationship of sleep quality and sleep duration with hypertension among adults aged 30-79 years old in Guangzhou.Methods:According to multi-stage stratified cluster sampling, 12 747 residents aged 30-79 years old were sampled and surveyed in Guangzhou from January 2018 to March 2019. Data on general demographic characteristics, sleep quality, sleep duration and hypertension were collected through questionnaire survey, the Pittsburgh sleep quality index (PSQI) and physical examination. Multivariate logistic regression models were used to analyze the putative association between sleep quality, sleep duration and hypertension. Restrictive cubic spline curve was used to draw the dose-response relationship curve between sleep quality, sleep time and hypertension.Results:The mean age of the subjects was (52.68±12.17) years, the prevalence of hypertension was 36.6% (4 664/12 747), the average score of PSQI was (4.70±2.88), and the average sleep time was (7.00±1.32) hours. The prevalence of hypertension was positively associated with the PSQI score. Compared to the subjects with a score less than 3, OR (95% CI) of hypertension with a PSQI score of 3-5, 5-8, ≥9 were 1.14 (1.02-1.27), 1.17 (1.03-1.34), 1.41 (1.21-1.64), respectively. The relationship between sleep duration and hypertension appeared U-shaped. Compared with 6 to 8 hours sleep duration, both sleep duration<6 hours with OR(95% CI) of 1.27(1.12-1.43) or >8 hours with OR(95% CI) of 1.20(1.05-1.38) was associated with hypertension. Conclusion:Both poor sleep quality, longer or shorter sleep duration were responsible for increased risk of cognitive impairment in older Chinese.

Objective:To investigate the predictive value of myoglobin (Mb) for the prognosis of sepsis related chronic critical illness (CCI).Methods:Retrospective study was conducted on septic patients with the length of ICU stay equal or greater than 14 days, and sepsis-related organ failure assessment (SOFA) score equal or greater than 2 on the 14th day in ICU in the First Department of Critical Care Medicine at the First Affiliated Hospital of Sun Yat-sen University from January 2017 to March 2020. Patients′ clinical and laboratory data were collected on the 1st and 14th day in ICU. The survival on day 28 in ICU was recorded. According to the myoglobin levels on day 1 and day 14, all subjects were divided into myoglobin elevation group and decline group. Kaplan-Meier survival curve was used to compare the cumulative survival rate at day 28. Cox regression analysis was used to analyze the independent risk factors of mortality. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of myoglobin.Results:A total of 131 patients with sepsis related CCI were recruited, including 58 patients in the elevation group and 73 in the decline group. The Mb level in elevation group on day 1 was significantly lower than that in decline group [172.40(59.99, 430.53) μg/L vs. 413.60(184.40, 1 328.50) μg/L, Z=3.749, P=0.000], and the Mb level on day 14 was the opposite change in two groups [483.65(230.38, 1 471.75)μg/L in elevation group vs. 132.20(76.86, 274.35)μg/L in decline group, Z=5.595, P=0.000]. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate of the elevation group was significantly lower than that of decline group (χ2=7.051, P=0.008). Cox ratio regression analysis suggested that elevated myoglobin was an independent risk factor for 28-day mortality in septic patients with CCI ( OR=2.534, 95% CI 1.212-5.295, P=0.013). ROC curve analysis suggested that the sensitivity of myoglobin elevation in predicting mortality related to CCI within 28 days was 64.5%, and the specificity was 32.0% with area under the curve(AUC) 0.661(95% CI 0.550-0.773, P=0.007) and Jorden Index was 0.325. Conclusion:Elevated myoglobin, an independent risk factor for mortality within 28 days in ICU, can predict the prognosis of sepsis related chronic critical illness.

Objective　To explore the characteristics of musical cognition in aged Cerebral Small Vessel Disease (CSVD) patients.Methods　Thirty-five aged CSVD individuals as well as 32 elderly subjects were recruited from Jan to Sep 2019 in Department of Neurology,the Seventh Medical Center for PLAGH.Montreal Battery of Evaluation of Amusia (MBEA) was chosen to analyze musical cognition,including pitch,rhythm and memory scores.Meanwhile,demographic data and amount of cognitive assessments were also collected.Student t-test for two independent samples was used to compare the data between groups,Pearson correlations were chosen to analyze the relationship between musical cognition parameters and other variants.Results　Compared to control group,aged CSVD individuals showed significant different ability of musical cognition,reflected by lower scores in pitch,rhythm and memory (P<0.05).Rhythm score correlated with Digital Symbol Substitution Test (DSST) (r=0.374,P=0.002).Memory score correlated with DSST (r=0.278,P=0.023) as well as Choice Reaction Time (CRT) (r=0.323,P=0.008).Total score correlated with DSST (r=0.338,P=0.005) as well as CRT (r=0.247,P=0.044).Conclusion　Significant differences could be found in musical cognition between aged CSVD patients and elderly control,and could be helpful to reveal the executive dysfunctions in aged CSVD subjects.

OBJECTIVE: To examine the effects of ethyl pyruvate (EP) on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)-induced human kidney-2 (HK-2) cells. METHODS: HK-2 cells were divided into three groups: HK-2 cells were challenged with LPS (800 μg/L) for 24 hours as LPS group, or LPS mixed with EP (0.25 mmol/L) for 24 hours as EP group. Cells were incubated with normal saline for 24 hours as control group. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intracellular adenosine triphosphate (ATP) were detected by enzyme linked immunosorbent assay (ELISA). JC-1 staining and Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assays were used to evaluate mitochondrial membrane potential and cell apoptosis, respectively. Western Blot was used to evaluate the protein expressions of mitochondrial dynamics, including death-associated protein kinase 2 (DAPK-2), mitofusin (Mfn-1 and Mfn-2), and apoptotic associated biomarkers, including caspase-3, caspase-9, Bcl-2, Bcl-xL, cytochrome C (Cyt C), and DNA repair enzyme poly ADP-ribose polymerase (PARP). RESULTS: Compared with the NC group, MDA, IL-6, TNF-α of LPS group were significantly increased, the expression of SOD, mitochondrial membrane potential and ATP level were significantly decreased, the expression of mitochondrial fission protein DAPK-2 was significantly increased, and mitochondrial fusion proteins Mfn-1 and Mfn-2 were significantly decreased, cell apoptosis and apoptotic protein caspase-3, caspase-9 and Cyt C were increased, and anti-apoptotic protein Bcl-2, Bcl-xL, PARP were significantly decreased. Compared with the LPS group, the oxidative activities and inflammatory factors above were inhibited in EP group [MDA (μmol/L): 12.35±2.21 vs. 45.95±1.76, SOD (kU/L): 54.68±1.42 vs. 40.73±1.60, IL-6 (ng/L): 67.87±2.61 vs. 338.92±20.91, TNF-α (ng/L): 19.23±1.80 vs. 180.69±6.51], mitochondrial membrane potential and ATP level were significantly increased [mitochondrial membrane potential: (99.43±0.25)% vs. (69.40±0.75)%, ATP (×10⁶ RLU): 0.19±0.01 vs. 0.12±0.05], the expression of mitochondrial fission protein was significantly decreased (DAPK-2/β-actin: 0.03±0.01 vs. 0.61±0.02), mitochondrial fusion proteins were significantly increased (Mfn-1/β-actin: 0.43±0.04 vs. 0.17±0.01, Mfn-2/β-actin: 0.201±0.004 vs. 0.001±0.001), percentage of cell apoptosis was significantly decreased [(5.25±0.17)% vs. (34.42±0.64)%], the expressions of apoptotic proteins were significantly decreased (caspase-3/β-actin: 0.25±0.15 vs. 1.76±0.01, caspase-9/β-actin: 0.09±0.02 vs. 1.52±0.12, Cyt C/β-actin: 0.001±0.001 vs. 0.350±0.030), and the expressions of anti-apoptotic proteins and PARP were significantly increased (Bcl-2/β-actin: 0.500±0.010 vs. 0.009±0.004, Bcl-xL/β-actin: 0.550±0.010 vs. 0.009±0.001, PARP/β-actin: 0.94±0.01 vs. 0.16±0.13), with statistically significant differences (all P < 0.05). CONCLUSIONS There are enhanced mitochondrial fission and diminished mitochondrial fusion in LPS-induced HK-2 cells. EP can protect mitochondria functions by regulate mitochondrial dynamics, and reducethe apoptosis of LPS-induced HK-2 cells.
Apoptosis ; Humans ; Kidney ; Lipopolysaccharides ; Mitochondrial Dynamics/drug effects* ; Protective Agents/pharmacology* ; Pyruvates/pharmacology*

Objective: To examine the effects of ethyl pyruvate (EP) on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)-induced human kidney-2 (HK-2) cells. Methods: HK-2 cells were divided into three groups: HK-2 cells were challenged with LPS (800 μg/L) for 24 hours as LPS group, or LPS mixed with EP (0.25 mmol/L) for 24 hours as EP group. Cells were incubated with normal saline for 24 hours as control group. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intracellular adenosine triphosphate (ATP) were detected by enzyme linked immunosorbent assay (ELISA). JC-1 staining and Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assays were used to evaluate mitochondrial membrane potential and cell apoptosis, respectively. Western Blot was used to evaluate the protein expressions of mitochondrial dynamics, including death-associated protein kinase 2 (DAPK-2), mitofusin (Mfn-1 and Mfn-2), and apoptotic associated biomarkers, including caspase-3, caspase-9, Bcl-2, Bcl-xL, cytochrome C (Cyt C), and DNA repair enzyme poly ADP-ribose polymerase (PARP). Results: Compared with the NC group, MDA, IL-6, TNF-α of LPS group were significantly increased, the expression of SOD, mitochondrial membrane potential and ATP level were significantly decreased, the expression of mitochondrial fission protein DAPK-2 was significantly increased, and mitochondrial fusion proteins Mfn-1 and Mfn-2 were significantly decreased, cell apoptosis and apoptotic protein caspase-3, caspase-9 and Cyt C were increased, and anti-apoptotic protein Bcl-2, Bcl-xL, PARP were significantly decreased. Compared with the LPS group, the oxidative activities and inflammatory factors above were inhibited in EP group [MDA (μmol/L): 12.35±2.21 vs. 45.95±1.76, SOD (kU/L): 54.68±1.42 vs. 40.73±1.60, IL-6 (ng/L): 67.87±2.61 vs. 338.92±20.91, TNF-α (ng/L): 19.23±1.80 vs. 180.69±6.51], mitochondrial membrane potential and ATP level were significantly increased [mitochondrial membrane potential: (99.43±0.25)% vs. (69.40±0.75)%, ATP (×10⁶ RLU): 0.19±0.01 vs. 0.12±0.05], the expression of mitochondrial fission protein was significantly decreased (DAPK-2/β-actin: 0.03±0.01 vs. 0.61±0.02), mitochondrial fusion proteins were significantly increased (Mfn-1/β-actin: 0.43±0.04 vs. 0.17±0.01, Mfn-2/β-actin: 0.201±0.004 vs. 0.001±0.001), percentage of cell apoptosis was significantly decreased [(5.25±0.17)% vs. (34.42±0.64)%], the expressions of apoptotic proteins were significantly decreased (caspase-3/β-actin: 0.25±0.15 vs. 1.76±0.01, caspase-9/β-actin: 0.09±0.02 vs. 1.52±0.12, Cyt C/β-actin: 0.001±0.001 vs. 0.350±0.030), and the expressions of anti-apoptotic proteins and PARP were significantly increased (Bcl-2/β-actin: 0.500±0.010 vs. 0.009±0.004, Bcl-xL/β-actin: 0.550±0.010 vs. 0.009±0.001, PARP/β-actin: 0.94±0.01 vs. 0.16±0.13), with statistically significant differences (all P < 0.05). Conclusions There are enhanced mitochondrial fission and diminished mitochondrial fusion in LPS-induced HK-2 cells. EP can protect mitochondria functions by regulate mitochondrial dynamics, and reducethe apoptosis of LPS-induced HK-2 cells.

Objective To investigate the effect and mechanism of miR-23b on the proliferation and migration of triple negative breast cancer (TNBC) cells.Methods Real time polymerase chain reaction (PCR) was used to detect the expression of miR-23b in triple negative breast cancer tissues.MDA-MB-231/miR-23b,BT549/miR-23b cell lines are constructed.Proliferation assay,scaling healing experiment and Transwell migration assay were used to detect the effect of miR-23b on the proliferation and migration of triple negative breast cancer cells.Dual-luciferase reporter gene assay was employed to examine the interactions between miR-23b and forkhead box C2 (FOXC2).Real time PCR and Western blot were performed to detect the effect of miR-23b on the expression of FOXC2.Results The expression level of miR-23b in triple negative breast cancer tissues was significantly less than that in adjacent normal tissues.miR-23b could reduced the proliferation and migration of triple negative breast cancer cells.Dual-luciferase assay confirmed that miR-23b could regulate the expression and activity of FOXC2.The expression of FOXC2 in mRNA and protein level was inhibited by miR-23b.Conclusions miR-23b can inhibit the expression of FOXC2 and affect the proliferation and migration of triple negative breast cancer cells.

Objective To establish a method to simultaneously determine syringing and isofraxidin by HPLC;To investigate the features of percutaneous absorption in vitro of Jiegugao blended and pasted by white vinegar, honey and vaseline; To discuss the mechanism of commonly used ointment matrices in Tujia Minority. Methods Rat abdomen skin in vitro was as transdermal barrier;the modified Franz diffusion pool was used to simulate human skin medication; the content of syringin and isoprofen was determined by HPLC; the percutaneous absorption equation was established and the related parameters, such as cumulative permeation rate and permeation rate, were calculated. Results When using Syncronis C18 (250 mm × 4.6 mm, 5 μm) as chromatographic column, acetonitrile-0.1%phosphoric acid as mobile phase, 1.0 mL/min as perfusion speed and 265 nm as determine wavelength, regression equation of syringingwas A=10 686.454 6C+1565.778 8 (r=1.000 0), regression equation of isofraxidin was A=12 297.305 4C-5913.729 9 (r=0.999 9). Cumulative permeation quantity of syringing in Jiegugao blended and pasted by white vinegar, honey, vaseline and blank were 7.549 2, 4.580 3, 3.890 8 and 5.378 4 μg?cm-2?h-1 respectively and permeation rate were 25.66%, 16.11%, 13.73% and 18.78%. Meanwhile, cumulative permeation quantity of isofraxidin were 2.536 9, 1.941 8, 1.178 2 and 2.293 6 μg?cm-2?h-1 respectively and permeation rate were 47.04%, 35.06%, 22.11%and 41.11%. Conclusion Using white vinegar as the ointment matrix can promote the percutaneous absorption of effective composition in Jiegugao blended. However, it will retard the percutaneous absorption of effective composition in Jiegugao when using honey and vaseline as the ointment matrices, but honey and vaseline can be used as a slow-release matrix.