ABSTRACT
BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P < 0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.
Subject(s)
Accidental Falls , Osteoporosis , Humans , Male , Aged , Osteoporosis/epidemiology , Osteoporosis/diagnosis , Retrospective Studies , Aged, 80 and over , Incidence , Risk Assessment/methods , Risk Factors , Comorbidity , China/epidemiology , Age FactorsABSTRACT
Transcutaneous immunization presents a major challenge on account of poor permeability of antigens through the skin barrier. To overcome this limitation, the deformable liposome could be a better method for transcutaneous delivery of these antigens. In this study, hepatitis B surface antigen (HBsAg) plasmid DNA-cationic complex deformable liposome was utilized as a mode for enhanced immunity against the antigen. Deformable liposome was prepared by conventional rotary evaporation method and characterized for various parameters such as vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity and stability. The immune stimulating activity was studied by measuring serum anti-HBsAg titre and cytokines level (interleukin-4 and interferon-gamma) following topical application of liposome in BALB/c mice and results were compared with deformable liposome encapsulated DNA applied topically as well as naked DNA and pure recombinant HBsAg, administered intramuscularly. It was observed that deformable liposome elicited a comparable serum antibody titre and endogenous cytokines levels compared to other vaccinations. The study signifies the potential of deformable liposome as DNA vaccine carriers for effective transcutaneous immunization.
Subject(s)
Antibodies/metabolism , DNA/administration & dosage , Hepatitis B Surface Antigens/genetics , Immunization/methods , Adjuvants, Immunologic , Administration, Cutaneous , Administration, Topical , Animals , Cell Membrane Permeability/physiology , DNA/immunology , Female , Hepatitis B Surface Antigens/immunology , Injections, Intramuscular , Interferon-gamma/metabolism , Interleukin-4/metabolism , Liposomes , Mice , Mice, Inbred BALB C , Skin/cytologyABSTRACT
In the present study, the relationship between PKB signaling and reactive oxygen species (ROS) during the course of exogenous and endogenous ROS or antioxidants regulating human 7721 hepatoma cell proliferation was studied. To change endogenous ROS levels, 7721 cells were transfected with human manganese superoxide dismutase (MnSOD) construct containing sense or antisense MnSOD cDNA. Low level of exogenous ROS H2O2(1-10 mumol/L) significantly stimulated PKB activity and c-fos/c-jun expression and cell growth, which could be abolished by antioxidant danshensu (40 mg/L). It was observed that overexpression of MnSOD inhibited 7721 cell growth by inhibiting PKB activity and c-fos/c-jun expression; the PKB activity and c-fos/c-jun expression, however, were stimulated by down-regulated MnSOD expression. In addition, PKB-7721 cells (transfected with sense PKB cDNA) promoted c-fos/c-jun expression by stimulating PKB activity. These results suggest that the redox state stimulated hepatoma cell growth through PKB pathway, which modulates AP-1 expression.
