The diverse life-course cohort (DLCC): protocol of a large-scale prospective study in China.

The Diverse Life-Course Cohort (DLCC) is a large-scale prospective study including around 130,000 participants in mainland China. The primary aims of DLCC include contributing to knowledge on noncommunicable chronic disease determinants, particularly cardiometabolic diseases, and exploring the long-term effect of ambient air pollutants or other environmental risk factors on health among all-age populations. The cohort consists of several sub-populations that cover the whole life-course and diverse resources: from premarital to adolescents, adults from workplace and communities ranged from 18 to 93 years old. Baseline assessment (2017-2021) included face-to-face standardized questionnaire interview and measurements to assess social and biological factors of health. Blood samples were collected from each participant (except for children younger than 6) to establish the biobank. DLCC consists of two visits. Visit 1 was conducted from 2017, and 114850 individuals from one of the world-class urban agglomerations: Beijing, Tianjin, and Hebei area were recruited. By the end of 2021, at least one follow-up was carried out, with an overall follow-up rate of 92.33%. In 2021, we initiated Visit 2, newly recruited 9,866 adults from Guangdong province (South China) and Hebei province (Central China), with research focuses on the comparations on ambient pollution hazards and other unique dietary or environmental risks for health. The baseline survey of Visit 2 was finished in July 2021. DLCC is still ongoing with a long-term follow-up design, and not limited by the current funding period. With reliable data and the well-established biobank which consists of over 120,000 individuals' blood samples, DLCC will provide invaluable resources for scientific research.

Effect of phenylephrine on alveolar fluid clearance in ventilator-induced lung injury.

OBJECTIVE: To investigate the effect of phenylephrine (an α-adrenergic agonist) on alveolar fluid clearance (AFC) in ventilator-induced lung injury and the possible mechanism involved. METHODS: A total of 170 male Wistar rats were randomly allocated into 17 groups (n=10) using random number tables. Short-term (40 minutes) mechanical ventilation with high tidal volume (HVT) was performed to induce lung injury, impair active Na+ transport and lung liquid clearance in the rats. Unventilated rats served as controls. To demonstrate the effect of phenylephrine on AFC, phenylephrine at different concentrations (1×10(-5), 1×10(-6), 1×10(-7), 1×10(-8), and 1×10(-9) mol/L) was injected into the alveolar space of the HVT ventilated rats. To identify the influence of adrenergic antagonists, Na(+) channel, and microtubular system on the effect of phenylephrine, phenylephrine at 1×10(-5) mol/L combined with prazosin (an α1-adrenergic antagonist, 1×10(-4) mol/L), yohimbine (an α2-adrenergic antagonist, 1×10(-4) mol/L), atenolol (a ß1- adrenergic antagonist, 1×10(-5) mol/L), ICI-118551 (an ß2-adrenergic antagonist, 1×10(-5) mol/L), amiloride (a Na+ channel blocker, 5×10(-4) mol/L), ouabain (a Na(+)/K(+)-ATPase blocker, 5×10(-4) mol/L), colchicine (a microtubular disrupting agent, 0.25 mg/100 g body weight), or ß-lumicolchicine (an isomer of colchicine, 0.25 mg/100 g body weight) were perfused into the alveolar space of the rats ventilated with HVT for 40 minutes. AFC and total lung water content were measured. RESULTS: Basal AFC in control rats was (17.47±2.56)%/hour, which decreased to (9.64± 1.32)%/hour in HVT ventilated rats (P=0.003). The perfusion of phenylephrine at 1×10(-8), 1×10(-7), 1×10(-6), and 1×10(-5) mol/L significantly increased the AFC in HVT ventilated rats (all P<0.05). This effect of phenylephrine on AFC was suppressed by prazosin, atenolol, and ICI-118551 in HVT ventilated rats by 53%, 31%, and 37%, respectively (all P<0.05). The AFC-stimulating effect of phenylephrine was lowered by 33% and 42% with amiloride and ouabain, respectively (both P<0.05). Colchicine significantly inhibited the effect of phenylephrine (P=0.031). CONCLUSION: Phenylephrine could increase the AFC in HVT-ventilated rats and accelerate the absorption of pulmonary edema.

Spousal Similarities in Cardiovascular Risk Factors in Northern China: A Community-Based Cross-Sectional Study.

Objectives: The aim of this study was to explore spousal similarities in cardiovascular risk factors in northern China. Methods: We conducted a cross-sectional study of married couples from Beijing, Hebei, Gansu, and Qinghai provinces between 2015 and 2019. A total of 2,020 couples were included in the final analyses. The spousal similarities for metabolic indicators and cardiovascular risk factors (including lifestyle factors and cardiometabolic diseases) were evaluated using Spearman's correlation and logistic regression analyses, respectively. Results: All metabolic indicators showed positive spousal correlations (p < 0.001), with the strongest for fasting blood glucose (r = 0.30) and the lowest for high-density lipoprotein cholesterol (r = 0.08). Significant husband-wife associations were observed for several cardiovascular risk factors except for hypertension in multivariable models, with the strongest association for physical inactivity (odds ratios with 95% confidence intervals of 3.59 [2.85, 4.52] and 3.54 [2.82, 4.46] for husbands and wives, respectively). In addition, the interaction of age with spousal overweight/obesity status was statistically significant, and the association was stronger in people ≥50 years. Conclusion: There were spousal similarities in cardiovascular risk factors. The finding may have public health implications that targeted screening and interventions for spouses of people with cardiovascular risk factors.

Prevalence of common chronic disease and multimorbidity patterns in Guangdong province with three typical cultures: analysis of data from the Diverse Life-Course Cohort study.

Background: Variations in the prevalence and pattern of multimorbidity might be attributable to lifestyle and environmental factors. This study was performed to determine the prevalence of common chronic diseases and to reveal multimorbidity patterns among adults in Guangdong province with Chaoshan, Hakka, and island cultures. Methods: We used data collected at the baseline survey (April-May 2021) of the Diverse Life-Course Cohort study and included 5,655 participants aged ≥20 years. Multimorbidity was defined as the presence of two or more of the 14 chronic diseases collected by self-reports, physical examinations, and blood tests. Multimorbidity patterns were explored by association rule mining (ARM). Results: Overall, 40.69% of participants had multimorbidity, and the prevalence among coastland (42.37%) and mountain residents (40.36%) was higher than that among island residents (37.97%). The prevalence of multimorbidity increased rapidly with higher age groups and showed an inflection point at 50 years, beyond which >50% of the middle-aged and older adults had multimorbidity. The proportion of people with two chronic diseases accounted for most cases of multimorbidity, and the strongest association was found between hyperuricemia and gout (lift of 3.26). The most prevalent multimorbidity pattern was dyslipidemia and hyperuricemia in the coastland areas and dyslipidemia combined with hypertension in the mountain and island areas. Furthermore, the most common triad combination consisted of cardiovascular diseases, gout, and hyperuricemia, which was verified in the mountain and coastal areas. Conclusion: These observations of multimorbidity patterns, including the most frequent multimorbidity and associations, will help healthcare providers develop healthcare plans that improve the effectiveness of multimorbidity management.

Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet.

Metabolic syndrome is a low-grade inflammatory state in which oxidative stress is involved. Naringin, isolated from the Citrussinensis, is a phenolic compound with anti-oxidative and anti-inflammatory activities. The aim of this study was to explore the effects of naringin on metabolic syndrome in mice. The animal models, induced by high-fat diet in C57BL/6 mice, developed obesity, dyslipidemia, fatty liver, liver dysfunction and insulin resistance. These changes were attenuated by naringin. Further investigations revealed that the inhibitory effect on inflammation and insulin resistance was mediated by blocking activation of the MAPKs pathways and by activating IRS1; the lipid-lowering effect was attributed to inhibiting the synthesis way and increasing fatty acid oxidation; the hypoglycemic effect was due to the regulation of PEPCK and G6pase. The anti-oxidative stress of naringin also participated in the improvement of insulin resistance and lipogenesis. All of these depended on the AMPK activation. To confirm the results of the animal experiment, we tested primary hepatocytes exposed to high glucose system. Naringin was protective by phosphorylating AMPKα and IRS1. Taken together, these results suggested that naringin protected mice exposed to a high-fat diet from metabolic syndrome through an AMPK-dependent mechanism involving multiple types of intracellular signaling and reduction of oxidative damage.

[Effects of Shengmai injection on testicular injury after torsion/detorsion in rats of different ages].

OBJECTIVE: To investigate the different effects of Shengmai injection on testicular injury after testis torsion/detorsion in rats of different ages. METHODS: Sixteen healthy male SD rats aged 3, 6 and 12 weeks were equally randomized into an experimental group (testicular torsion/detorsion plus Shengmai injection) and a control group (testicular torsion/detorsion plus saline). The rat models of testicular torsion were killed 24 h after surgery for the measurement of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis. RESULTS: Compared with the controls, the 3- and 6-week-old rats of the experimental group showed no significant changes in T-AOC, SOD activity and MDA content (P > 0.05), while the 12-week-old experimental rats exhibited a remarkable increase in SOD and T-AOC and an obvious decrease in MDA content (P < 0.05). CONCLUSION: Shengmai injection has a protective effect against acute ischemia-reperfusion testicular injury after torsion/detorsion in rats, but the effect varies with the age, more obvious in older ones.

Bistriazoles with a Biphenyl Core Derivative as an Electron-Favorable Bipolar Host of Efficient Blue Phosphorescent Organic Light-Emitting Diodes.

High-quality host materials are indispensable for the construction in the emitting layer of efficient organic light-emitting diodes (OLEDs), especially in a guest and host system. The good carrier transport and energy transfer between the host and emitters are out of necessity. In this work, a wide bandgap and bipolar organic compound, 2,2'-bis(4,5-diphenyl-(1,2,4)-triazol-3-yl)biphenyl (BTBP), conjugating two electron-transporting triazole moieties on a hole-transporting biphenyl core, was synthesized and characterized. The wide bandgap of 4.0 eV makes the promise in efficient energy transfer between the host and various color emitters to apply as the universal host, especially for blue emitters. The close electron and hole mobilities perform the same order of 10-5 cm2·V-1·s-1, identified as bipolar behavior and benefited for carrier balance at low bias. Although carrier transportation belongs to bipolar behavior at a low electrical field, the electron mobility is much faster than the hole one at a high electrical field and belongs to electron-transporting behavior. Employing the BTBP as the host matrix mixed with a phosphor dopant, iridium(III)bis[4,6-di-fluorophenyl-pyridinato-N,C2]picolinate, a high-efficiency sky-blue phosphorescent organic light-emitting diode (OLED) was achieved with a maximum current efficiency of 65.9 cd/A, maximum power efficiency of 62.8 lm/W, and maximum external quantum efficiency of 30.2%.

Pseudolaric acid B induces caspase-dependent cell death in human ovarian cancer cells.

Pseudolaric acid B (PAB) is a diterpene acid isolated from the root and trunk bark of Pseudolarix kaempferi Gordon (Pinaceae). Recent studies have reported that PAB exhibits cytotoxic effects in several cancer cell lines. In the present study, we assessed its antitumor activity and molecular mechanisms in HO-8910 and A2780 ovarian cancer cells in vitro. We found that PAB reduced cell viability and induced apoptosis in a dose- and time-dependent manner in HO-8910 and A2780 human ovarian cancer cells. The induction of apoptosis was also accompanied by the regulation of Bcl-2 and XIAP family proteins, cytochrome c and Apaf-1. Moreover, we observed that PAB treatment resulted in the activation of caspase-3 and -9, which may partly explain the anticancer activity of PAB. Collectively, the present study for the first time suggests that PAB enhances apoptosis of HO-8910 and A2780 cells through regulation of Bcl-2 and IAP family proteins. Moreover, the triggering of caspase-3 and -9 activation mediated apoptotic induction. Our results suggest that PAB may be a new therapeutic option for the treatment of ovarian cancers.

Pseudolaric acid B induces apoptosis in U937 human leukemia cells via caspase-9­mediated activation of the mitochondrial death pathway.

Numerous studies have demonstrated that pseudolaric acid B (PAB) promotes apoptosis in several cancer cell lines. However, thus far, the effect of PAB on human leukemia cells has not been evaluated. In the present study, the antitumor activity and molecular mechanisms of PAB in human leukemia U937 cells were investigated. It was demonstrated that PAB induced U937 cell apoptosis, which was confirmed by typical morphological changes and Annexin V­fluorescein isothiocyanate staining. PAB was observed to activate a caspase­dependent apoptotic pathway in U937 cells through the regulation of the Bcl­2 family protein-mediated mitochondrial pathway. Furthermore, the activities of caspase­3 and -9 were increased following treatment with PAB. In conclusion, to the best of our knowledge, this study demonstrated for the first time that PAB was able to enhance the apoptosis of U937 cells, at least in part, through the activation of the mitochondrial death pathway. Moreover, the activation of caspase­3 and -9 mediated the apoptotic induction.

Effect of beta3-adrenergic agonists on alveolar fluid clearance in hypoxic rat lungs.

BACKGROUND: Recent research suggests that beta(2)-adrenergic agonists increase alveolar fluid clearance (AFC) under physiologic and pathologic conditions. It is unknown whether beta(3)-adrenergic agonists also increase AFC under pathologic conditions. The aim of this study was to investigate the effect of beta(3)-adrenergic agonists on AFC following hypoxic lung injury and the mechanisms involved. METHODS: Hypoxic rats were exposed to 10% oxygen. BRL-37344 (beta(3)-adrenergic agonist) or CGP-12177 (selective beta(3)-adrenergic agonist) alone or combined with beta receptor antagonists, sodium channel blockers, or Na(+)/K(+)-ATPase blockers were perfused into the alveolar space of rats exposed to 10% oxygen for 48 hours. Total lung water content (TLW) and AFC were measured. RESULTS: AFC did not change for the first 24 hours but then decreased after 48-hour exposure to 10% oxygen. The perfusion of BRL-37344 or CGP-12177 significantly increased AFC in normal and hypoxic rats. The AFC-stimulating effect of CGP-12177 was lowered with amiloride (a Na(+) channel blocker) and ouabain (a Na(+)/K(+)-ATPase inhibitor) by 37% and 49%, respectively. Colchicine significantly inhibited the effect of CGP-12177. CONCLUSIONS: These findings suggest that beta(3)-adrenergic agonists can increase AFC during hypoxic lung injury in rats and accelerate the amelioration of pulmonary edema.

Plasma metabolic profiling of Alzheimer's disease by liquid chromatography/mass spectrometry.

OBJECTIVES: The identification of Alzheimer's disease (AD) biomarkers may allow for a less invasive and more accurate diagnosis as well as serve as a predictor of future disease progression and treatment response. The aim of this study was to map potential biomarkers in plasma for AD. DESIGN AND METHODS: Plasma metabolic perturbations between AD and healthy old person were investigated using ultra performance liquid chromatography/mass spectrometry (UPLC/MS) and metabonomics approach. The principal component analysis (PCA) of UPLC/MS spectra showed that metabolic changes between two groups. RESULTS: The PCA of UPLC/MS spectra showed that metabolic changes observed between AD and control were clear. Nine potential biomarkers in correlation with the extent of AD were found. CONCLUSIONS: Based on PCA, several potential biomarkers (LPCs, sphingosine and tryptophan) were found and further identified by the following LC/MS/MS analysis. All of them could be the potential early markers of AD.