Age of Retirement and Human Capital in an Aging China, 2015-2050.

As China continues to age rapidly, whether the country should adjust the official retirement age, and if so, when and how, are currently major policy concerns. We examine the impact of postponing the retirement age on the human capital of China in the next four decades. Two critical aspects of human capital-health and education-are incorporated to account for the quality of the work force. Our projections reveal the impact of nine scenarios on the Chinese labor force in the next few decades, highlighting the changes in "the high human capital workforce"-those with good health and education. We show substantial impact with added work force ranging from 28 to 92 million per year depending on which scenarios are implemented. Furthermore, the retained workers are increasingly better educated. The gain in female workers is particularly significant, reaping the benefits of the education expansion since the 1990s.

Oxidative stress regulates mitogen­activated protein kinases and c­Jun activation involved in heat stress and lipopolysaccharide­induced intestinal epithelial cell apoptosis.

Heat stress and gut­derived endotoxinemia are common causes of multiple organ dysfunction syndrome in heat stroke patients. Evidence has demonstrated that cell apoptosis in the small intestine serves an important role in the pathogenesis of heatstroke, which leads to increased intestinal permeability to endotoxin or lipopolysaccharides (LPS) from the gut entering the circulation. However, little is known about the potential underlying mechanisms mediating heat stress combined with LPS­induced intestinal epithelial cell apoptosis. In the present study, LPS combined with heat stress induced production of reactive oxygen species (ROS), mitochondrial membrane potential disruption and cell apoptosis, which eventually led to increased intestinal permeability and reduced epithelial resistance in the IEC­6 cell line. Inductions in ROS, mitochondrial membrane potential disruption and cell apoptosis were detected by using an ROS assay kit, 5,5',6,6'­tetrachloro­1,1',3,3'tetraethylbenzimidazo carbocyanine iodide dye kit and annexin V­fluorescein isothiocyanate apoptosis kit, respectively. The effect of ROS on mitogen activated protein kinases (MAPKs) and c­Jun activation was investigated using the antioxidant drug, butylated hydroxyanisole (BHA) by western blotting. The results of the present study demonstrated that ROS is essential to activate p38, extracellular signal­regulated kinase (ERK) and c­Jun, but not c­Jun N­terminal kinase (JNK), in LPS combined with heat stress treated cells. Furthermore, ROS, and activation of p38, JNK and c­Jun, were revealed to serve pro­apoptosis roles which aggravated damage to epithelial barrier integrity, as assessed by flow cytometry using Annexin V­fluorescein isothiocyanate staining and pretreatment of cells with specific inhibitors of ROS, JNK, p38 and c­Jun (BHA, SP600125, SB203580 and c­Jun peptide, respectively). Transepithelial electrical resistance and horseradish peroxidase permeability were detected in cells treated with LPS combined with heat stress, which revealed that ERK serves an anti­apoptosis role, as determined by pretreatment of cells with PD98059, a specific inhibitor of ERK. In conclusion, these findings suggested a novel role of the ROS signaling pathway which involved activation of MAPKs and c­Jun, following LPS combined with heat stress­induced IEC­6 cell apoptosis and impairment of the epithelial barrier. These results may facilitate understanding of pathological conditions involving ROS, such as heat stroke.

PAR1­mediated c­Jun activation promotes heat stress­induced early stage apoptosis of human umbilical vein endothelial cells.

Our previous study indicated that when human umbilical vein endothelial cells (HUVECs), which are involved in endothelial barrier function, are heat stressed, levels of protease­activated receptor 1 (PAR1) are increased significantly. In the present study, it was demonstrated that PAR1 serves a vital role in heat stress­induced HUVEC apoptosis. When the PAR1 inhibitor, SCH79797 (SCH), or a small interfering RNA (siRNA) targeting PAR1 were used to inhibit PAR1 signaling, a marked decrease in cell apoptosis, caspase­3 activity and the expression of the pro­apoptotic protein B­cell lymphoma 2 (Bcl­2) associated X (Bax), as well as increased expression of the anti­apoptotic Bcl­2 family member, myeloid cell leukemia 1 (Mcl­1), were observed. In addition, heat stress­induced apoptosis, caspase­3 activity and the expression of Bax were significantly increased following administration of the PAR1 agonist, TFLLR­NH2 or adenovirus overexpression of PAR1. This was accompanied by decreased protein expression levels of Mcl­1. Furthermore, it was identified that the DNA binding activity of the nuclear factor (NF)­κB p65 subunit increased and c­Jun activation was reduced as a result of inhibition of PAR1 signaling by SCH or siRNA­mediated PAR1 knockdown in heat stress­induced HUVECs. Additionally, our previous study reported that NF­κB p65 activation may have an anti­apoptosis effect on heat stressed HUVECs, whereas in the present study c­Jun activation had a pro­apoptosis effect on heat stressed HUVECs. Taken together, these results indicated that PAR1 signaling­mediated c­Jun activation promotes early apoptosis of HUVEC cells induced by heat stress.

NF-κB signaling is essential for resistance to heat stress-induced early stage apoptosis in human umbilical vein endothelial cells.

Cell apoptosis induced by heat stress is regulated by a complex signaling network. We previously reported that a p53-dependent pathway is involved. Here, we present evidence that NF-κB signaling plays a crucial role in preventing heat stress-induced early apoptosis. Human umbilical vein endothelial cells (HUVECs) were examined and increased phosphorylation of p65 and IκBα were detected, without IκBα degradation. When NF-κB signaling was inhibited by BAY11-7082, or a small interference RNA (siRNA) targeting p65, a significant increase in cell apoptosis and caspase-3 activity was observed, as well as reduced expression and translocation of HSP27 into the nucleus, an accumulation of reactive oxygen species, and prolonged phosphorylation of mitogen-activated protein kinases (MAPKs). In addition, an association between HSP27 and p65 was identified which may enhance NF-κB activation. When HSP27 was overexpressed, pretreatment of HUVECs with the antioxidant, apocynin, or N-acetyl cysteine, suppressed apoptosis. Similarly, inhibition of JNK and p38 with SP600125 and SB203580, respectively, also suppressed apoptosis, whereas siRNA-mediated HSP27 knockdown and treatment with the ERK 1/2 inhibitor PD98059 did otherwise. In conclusion, these findings suggest a novel role for an NF-κB signaling pathway involving HSP27, ROS, and MAPKs that confers a protective effect against heat stress-induced cell apoptosis.

[Protective effects of ulinastatin against acute lung injury induced by heatstroke in mice].

OBJECTIVE: To investigate the protective effect of ulinastatin (UTI) against acute lung injury induced by heatstroke in mice. METHODS: Sixty C57/BL6 mice were randomly divided into 6 groups, with 10 mice in each: control group, heatstroke group, UTI pretreatment group, saline pretreatment group, UTI post-treatment group, saline post-treatment group. The control mice were housed at a controlled room temperature of (22∓1) degrees; celsius, and the other groups were placed inside a temperature and humidity controlled chamber pre-set at 37 degrees; celsius and 60%. The two UTI groups were intraperitoneally injected with UTI at 5×10(4) U/kg 10 min before or after heat stress, and the two saline groups were given then equal amounts of saline in the same manner. The core body temperature of mice was monitored by a mercury thermometer every 30 min in the first 1.5 h during heating. The core temperature was measured, then every 15 min until it reached 42.7 degrees; celsius, which was taken as the onset of heatstroke. The animals were allowed to recover passively at ambient temperature for 6 h. The lung histopathological changes, protein concentration in BALF, lung wet/dry weight ratios, lung water content, and pulmonary microvascular permeability were assayed after 6 h of recovery at 37 degrees;celsius. RESULTS: Compared with the control group, the heatstroke model group and two saline groups displayed more severe lung damage and pathological morphology changes, and the lung wet/dry weight ratio, protein concentration in BALF, lung water content and pulmonary microvascular permeability were also significantly increased. These effects were significantly alleviated in UTI treated group. Pretreat ment with UTI significantly prolonged the time to Tc≥42.7 degrees; celsius but had no effect on lung injury induced by heatstroke. CONCLUSION: UTI can reduce the pulmonary edema and inflammatory exudation in acute lung injury caused by heatstroke.

[Mechanism of continuous venovenous hemofiltration combined with ulinastatin for the treatment of septic shock].

OBJECTIVE: To investigate the molecular mechanisms of continuous venovenous hemofiltration (CVVH) combined with ulinastatin (ULI) (CVVH-ULI) for the treatment of septic shock. METHODS: Human umbilical endothelial cells (HUVECs) were incubated with serums isolated from normal healthy people (control), septic shock patients treated with conventional therapy (CT) or treated with CVVH combined with ULI (CVVH-ULI). Endothelial permeability was evaluated by the leakage of FITC-labeled albumin. The morphological changes of F-actin was evaluated by Rhodamine-phalloidin. The phosphorylated levels of p38 were determined by Western blot. Cells were then treated with p38inhibitor (SB203580), or DMSO, followed by incubation with serum from septic shock patients treated with conventional therapy. Endothelial permeability and F-actin rearrangements were also evaluated as noted above. RESULTS: Serum from CT group increased endothelial permeability, F-actin rearrangements, and phosphorylated levels of p38, which were inhibited by CVVH-ULI treatment. Moreover, in CT group, the serum-induced endothelial hyperpermeability and F-actin rearrangements were inhibited by SB203580, the inhibitor of p38. CONCLUSION: CVVH combined with ulinastatin decreases endothelial hyperpermeability induced by septic shock through inhibiting p38 MAPK pathways.

Heat stress-induced disruption of endothelial barrier function is via PAR1 signaling and suppressed by Xuebijing injection.

Increased vascular permeability leading to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is central to the pathogenesis of heatstroke. Protease-activated receptor 1 (PAR1), the receptor for thrombin, plays a key role in disruption of endothelial barrier function in response to extracellular stimuli. However, the role of PAR1 in heat stress-induced endothelial hyper-permeability is unknown. In this study, we measured PAR1 protein expression in heat-stressed human umbilical venous endothelial cells (HUVECs), investigated the influences of PAR1 on endothelial permeability, F-actin rearrangement, and moesin phosphorylation by inhibiting PAR1 with its siRNA, neutralizing antibody (anti-PAR1), specific inhibitor(RWJ56110), and Xuebijing injection (XBJ), a traditional Chinese medicine used for sepsis treatment, and evaluated the role of PAR1 in heatstroke-related ALI/ARDS in mice by suppressing PAR1 with RWJ56110, anti-PAR1and XBJ. We found that heat stress induced PAR1 protein expression 2h after heat stress in endothelial cells, caused the release of endothelial matrix metalloprotease 1, an activator of PAR1, after 60 or 120 min of heat stimulation, as well as promoted endothelial hyper-permeability and F-actin rearrangement, which were inhibited by suppressing PAR1 with RWJ56110, anti-PAR1 and siRNA. PAR1 mediated moesin phosphorylation, which caused F-actin rearrangement and disruption of endothelial barrier function. To corroborate findings from in vitro experiments, we found that RWJ56110 and the anti-PAR1 significantly decreased lung edema, pulmonary microvascular permeability, protein exudation, and leukocytes infiltrations in heatstroke mice. Additionally, XBJ was found to suppress PAR1-moesin signal pathway and confer protective effects on maintaining endothelial barrier function both in vitro and in vivo heat-stressed model, similar to those observed above with the inhibition of PAR1. These results suggest that PAR1 is a potential therapeutic target in heatstroke.

Implications of changes in households and living arrangements for future home-based care needs and costs for disabled elders in China.

OBJECTIVES: To better understand future home-based care needs and costs for disabled elders in China. METHOD: To further develop and apply the ProFamy extended cohort-component method and the most recent census and survey data. RESULTS: (a) Chinese disabled elders and the annual growth rate of the percentage of national gross domestic product (GDP) devoted to home-based care costs for disabled elders will increase much more rapidly than the growth of total elderly population; (b) home-based care needs and costs for disabled oldest-old aged 80+ will increase much faster than that for disabled young-old aged 65-79 after 2030; (c) disabled unmarried elders living alone and their home-based care costs increase substantially faster than those disabled unmarried elders living with children; (d) percent of rural disabled oldest-old will be substantially higher than that of rural population after 2030; (e) sensitivity analyses show that possible changes in mortality and elderly disability status are the major direct factors affecting home-based care needs and costs; (f) caregivers resources under the universal two-child policy will be substantially better than that under the rigorous fertility policy unchanged. DISCUSSION: We discuss policy recommendations concerning pathways to healthy aging with relatively reduced care costs, including reductions of the prevalence of disability, gender equality, the universal two-child policy and resources of caregivers, encouragements of rural-to-urban family migration and elder's residential proximity to their adult children, and remarriages of not-married elders.

Household and living arrangement projections at the subnational level: an extended cohort-component approach.

This article presents the core methodological ideas and empirical assessments of an extended cohort-component approach (known as the "ProFamy model"), and applications to simultaneously project household composition, living arrangements, and population sizes-gender structures at the subnational level in the United States. Comparisons of projections from 1990 to 2000 using this approach with census counts in 2000 for each of the 50 states and Washington, DC show that 68.0 %, 17.0 %, 11.2 %, and 3.8 % of the absolute percentage errors are <3.0 %, 3.0 % to 4.99 %, 5.0 % to 9.99 %, and ≥10.0 %, respectively. Another analysis compares average forecast errors between the extended cohort-component approach and the still widely used classic headship-rate method, by projecting number-of-bedrooms-specific housing demands from 1990 to 2000 and then comparing those projections with census counts in 2000 for each of the 50 states and Washington, DC. The results demonstrate that, compared with the extended cohort-component approach, the headship-rate method produces substantially more serious forecast errors because it cannot project households by size while the extended cohort-component approach projects detailed household sizes. We also present illustrative household and living arrangement projections for the five decades from 2000 to 2050, with medium-, small-, and large-family scenarios for each of the 50 states; Washington, DC; six counties of southern California; and the Minneapolis-St. Paul metropolitan area. Among many interesting numerical outcomes of household and living arrangement projections with medium, low, and high bounds, the aging of American households over the next few decades across all states/areas is particularly striking. Finally, the limitations of the present study and potential future lines of research are discussed.

A Multistate Life Table Analysis of Union Regimes in the United States: Trends and Racial Differentials, 1970-2002.

We estimate trends and racial differentials in marriage, cohabitation, union formation and dissolution (union regimes) for the period 1970-2002 in the United States. These estimates are based on an innovative application of multistate life table analysis to pooled survey data. Our analysis demonstrates (1) a dramatic increase in the lifetime proportions of transitions from never-married, divorced or widowed to cohabiting; (2) a substantial decrease in the stability of cohabiting unions; (3) a dramatic increase in mean ages at cohabiting after divorce and widowhood; (4) a substantial decrease in direct transition from never-married to married; (5) a significant decrease in the overall lifetime proportion of ever marrying and re-marrying in the 1970s to 1980s but a relatively stable pattern in the 1990s to 2000-2002; and (6) a substantial decrease in the lifetime proportion of transition from cohabiting to marriage. We also present, for the first time, comparable evidence on differentials in union regimes between four racial groups.