The spatio-temporal pattern and its influencing factors of production efficiency of health resources in China

There is always a contradiction between the limited health resources and the unlimited demand of the population for health services, and only by improving the productivity of health resources can the health level of the population be improved as much as possible. Using prefecture-level administrative regions as spatial units, the paper analyzes the spatial pattern and changes of health productivity of health resources in China from 2000 to 2010, and uses a spatial panel Tobit model to examine the effects of factors such as technical level of health institutions, health service accessibility, public health policies and ecological environment quality on health productivity of health resources. The results show that with the Hu Huanyong line as the dividing line, the spatial heterogeneity of “high in the southeast and low in the northwest” in the health productivity of China's health resources is clear; as the regional differences narrow, the spatial correlation increases, and the spatial pattern of “overall dispersion and partial agglomeration” becomes more obvious. The fitting results of the spatial Durbin model reveal the direction and degree of influence of local and adjacent factors on the production efficiency of health resources. The positive influence of technical level of local health institutions and the accessibility of health services, the literacy level and the ability to pay for health services of residents in adjacent areas, the degree of urbanization of regional health resource allocation, climate suitability and the quality of the atmospheric environment are significant. And the negative influence of local residents' literacy and ability to pay for health services, the technical level of health institutions in adjacent areas and the degree of medicalization of health resource allocation are also significant. The influence of the degree of medicalization of local health resource allocation and the accessibility of health services in adjacent areas are significantly spatial-heterogeneous

Catalytic Mechanism of Amyloid-β Peptide Degradation by Insulin Degrading Enzyme: Insights from QM/MM MP2 Calculation

Insulin degrading enzyme (IDE), a metalloprotease that degrades amyloid-β (Aβ) peptides and insulin, is associated with Alzheimer’s disease and diabetes. The mechanism of IDE catalyzed degrading of Aβ peptides, which is of fundamental importance in the design of therapeutic methods for Alzheimer’s disease, has not been fully understood. In this work, combined quantum mechanics and molecular mechanics (QM/MM) style Møller-Plesset second order perturbation theory (MP2) geometry optimization calculations are performed to investigate the catalytic mechanism of the Aβ40 Phe19-Phe20 peptide bond cleavage by human IDE. The analyses using QM/MM MP2 optimization suggest that a neutral water molecule is at the active site of the enzyme-substrate (ES) complex. The water molecule is in hydrogen bonding with the nearby anionic Glu111 of IDE, but not directly bound to the catalytic Zn ion. This is confirmed by QM/MM DFTB3 molecular dynamics simulation. Our studies also reveal that the hydrolysis of the Aβ40 Phe19-Phe20 peptide bond by IDE consists of four key steps. The neutral water is first activated by moving toward and binding to the Zn ion. A gem-diol intermediate is then formed by the activated neutral water molecule attacking the C atom of the Phe19-Phe20 peptide bond. The next is the protonation of the N atom of Phe19-Phe20 peptide bond to form an intermediate with an elongated C-N bond. The final step is the breaking of the Phe19-Phe20 C-N bond. The final step is the rate-determining step with a calculated Gibbs free energy of activation of 17.34 kcal/mol, in good agreement with the experimental value 16.7 kcal/mol. This mechanism provides the basis for the design of biochemical methods to modulate the activity of IDE in humans

Relationship between serum albumin and pulse wave velocity in patients on continuous ambulatory peritoneal dialysis

Li-Tao Cheng1, Li-Jun Tang1,2, Hui-Min Chen1,3, Wen Tang1, Tao Wang11Division of Nephrology, Peking University Third Hospital, Beijing, China; 2Division of Nephrology, Qilu Hospital of Shandong University, Ji’nan, China; 3Division of Cardiology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, ChinaBackground: Hypoalbuminemia is a risk factor for cardiovascular events and mortality in dialysis patients, but the underlying mechanism remains unclear. Meanwhile, increased pulse wave velocity (PWV), the marker of arterial stiffness, has been proved to be an independent predictor of cardiovascular disease. The relationship between serum albumin and PWV in continuous ambulatory peritoneal dialysis patients (CAPD) was studied.Methods: Sixty-two CAPD patients were studied. The average age was 63 ± 12 years and dialysis duration was 23 ± 22 months. Serum albumin, C-reactive protein (CRP), and carotid-femoral PWV were measured.Results: Among these patients, 43.5% were men. The mean serum albumin concentration was 37 ± 4 g/L and PWV was 11.9 ± 2.3 m/s. PWV positively correlated with age (r = 0.35, P < 0.01), diabetes (yes = 1, no = 0; r = 0.292, P < 0.05), systolic blood pressure (SBP; r = 0.493, P < 0.001) and CRP (r = 0.295, P < 0.05), but negatively correlated with serum albumin (r = −0.357, P < 0.01). In multiple regression analysis, SBP (β = 0.615, P < 0.001), age (β = 0.414, P < 0.01), albumin (β = −0.315, P < 0.05) and total cholesterol (β = 0.275, P < 0.05) were independent determinants of PWV. In a non-inflamed subgroup (CRP < 3 mg/L, n = 30), albumin still negatively correlated with PWV (r = −0.66, P < 0.001).Conclusion: Serum albumin inversely correlated with increased PWV in CAPD patients, suggesting that increased arterial stiffness might be the link between hypoalbuminemia and increased cardiovascular mortality in dialysis patients.Keywords: hypoalbuminemia, cardiovascular events, pulse wave velocity, arterial stiffness, peritoneal dialysi