Effect of Modifiable Lifestyle Factors on Biological Aging.

Biological age is a concept that uses bio-physiological parameters to account for individual heterogeneity in the biological processes driving aging and aims to enhance the prediction of age-related clinical conditions compared to chronological age. Although engaging in healthy lifestyle behaviors has been linked to a lower mortality risk and a reduced incidence of chronic diseases, it remains unclear to what extent these health benefits result from slowing the pace of the biological aging process. This short review summarized how modifiable lifestyle factors - including diet, physical activity, smoking, alcohol consumption, and the aggregate of multiple healthy behaviors - were associated with established estimates of biological age based on clinical or cellular/molecular markers, including Klemera-Doubal Method biological age, homeostatic dysregulation, phenotypic age, DNA methylation age, and telomere length. In brief, the available studies tend to show a consistent association of lifestyle factors with physiological measures of biological age, while findings regarding molecular-based metrics vary. The limited evidence highlights the need for further research in this field, particularly with a life-course approach.

Dose-Responsive Impacts of Social Frailty on Intrinsic Capacity and Healthy Aging among Community-Dwelling Middle-aged and Older Adults: Stronger Roles of Social Determinants over Biomarkers.

OBJECTIVE: The intricate relationship between social determinants, e.g., social frailty, biomarkers and healthy aging remains largely unexplored, despite the potential for social frailty to impact both intrinsic capacity (IC) and functional ability in the aging process. DESIGN: Retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: Participants aged 50+ years from the Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan, stratified into three age groups: 50-64, 65-74 and 75+. MEASUREMENTS: Social frailty was defined based on a score derived from four domains: exclusion from general resources, social resources, social activity, and fulfillment of basic social needs. The scores were categorized as score=0 (no social frailty), 1 (social pre-frailty), and 2+ (social frailty). Multivariable logistic regression and Cox proportional hazard models were employed to examine the dose-responsive relationship between social frailty, low IC, functional and psychological health, and mortality. RESULTS: Of 1015 study participants, 24.9% and 7.9% were classified as social pre-frailty and social frailty, respectively. No significant differences were observed in most biomarkers between those with social frailty and those without. A dose-responsive relationship was found between social frailty and increased risk of low IC (social pre-frailty: aOR 2.20 [95% CI 1.59-3.04]; social frailty: 5.73 [3.39-9.69]). Similar results were found for functional and psychological health. However, no significant association between social frailty and all-cause mortality was found at the 4-year follow-up (social pre-frailty: aHR 1.52 [95% CI 0.94-2.43]; social frailty: 1.59 [0.81-3.09]). CONCLUSIONS: The significant association between social frailty and low IC, functional limitations, cognitive declines, and depressive symptoms underscores the pressing need for research on intervention strategies to enhance healthy aging in the lifespan course.

Intrinsic Capacity Impairment Patterns and their Associations with Unfavorable Medication Utilization: A Nationwide Population-Based Study of 37,993 Community-Dwelling Older Adults.

OBJECTIVES: Our aim was to explore the patterns of intrinsic capacity (IC) impairments among community-dwelling older adults and the associations of these different patterns with excessive polypharmacy, potentially inappropriate medications, and adverse drug reactions in a nationwide population-based study. DESIGN: A cross-sectional study included older adults from the Taiwan Integrated Care for Older People (ICOPE) program in 2020. SETTING AND PARTICIPANTS: The study subjects comprised 38,308 adults aged 65 years and older who participated in the ICOPE Step 1 screening and assessed six domains of IC following the World Health Organization (WHO) ICOPE approach. METHODS: Latent class analysis was adopted to identify distinct subgroups with different IC impairments patterns. The associations between different IC impairments patterns and unfavorable medication utilization, including excess polypharmacy (EPP), potentially inappropriate medications (PIMs), and adverse drug reactions (ADRs), were assessed by multivariate logistic regression models. RESULTS: Latent class analysis identified five distinct subgroups with different IC impairment patterns: robust (latent class prevalence: 59.4%), visual impairment (17.7%), physio-cognitive decline (PCD) with sensory impairment (12.3%), depression with cognitive impairment (7.7%), and impairments in all domains (2.9%). Compared to the robust group, all other groups were at higher odds for unfavorable medication utilization. The "depression with cognitive impairment" group (EPP: aOR=4.35, 95% CI 3.52-5.39, p<0.01; PIMs: aOR=2.73, 95% CI 2.46-3.02, p<0.01) and the "impairment in all domains" group (EPP: aOR=9.02, 95% CI 7.16-11.37, p<0.01; PIMs: aOR=3.75, 95% CI 3.24-4.34, p<0.01) remained at higher odds for EPP and PIMs after adjustment. CONCLUSIONS: We identified five distinct impairment patterns of IC, and each impairment pattern, particularly the "depression with cognitive impairment" and "impairment in all domains", was associated with higher odds of EPP and PIMs. Further longitudinal and intervention studies are needed to explore long-term outcomes of different impairment pattern and their reversibility.

Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study.

BACKGROUND: Frailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses - disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different. OBJECTIVES: The aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults. MATERIAL AND METHODS: We performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET). RESULTS: Although not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [ß = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [ß = -2.42 (-4.76, -0.08)], Omega 3 Index [ß = -0.50 (-0.95, -0.06)] and hippocampal volume [ß = -0.22 (-0.42,-0.02)]. They also had higher values of GDF15 [ß = 246.1 (88.9, 403.4)] and TNFR1 [ß = 157.5 (7.8, 307.2)]. CONCLUSION: Age-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.

[A descriptive analysis on type 2 diabetes in twins in China].

Objective: To describe the distribution characteristics of type 2 diabetes in twins in Chinese National Twin Registry (CNTR), provide clues and evidence for revealing the influence of genetic and environmental factors for type 2 diabetes. Methods: Of all twins registered in the CNTR during 2010-2018, a total 18 855 twin pairs aged ≥30 years with complete registration information were included in the analysis. The random effect model was used to describe the population and area distribution characteristics and concordance of type 2 diabetes in twin pairs. Results: The mean age of the subjects was (42.8±10.2) years, the study subjects included 10 339 monozygotic (MZ) twin pairs and 8 516 dizygotic (DZ) twin pairs. The self-reported prevalence rate of type 2 diabetes was 2.2% in total population and there was no sighificant difference between MZ and DZ. Intra-twin pairs analysis showed that the concordance rate of type 2 diabetes was 38.2% in MZ twin pairs, and 16.0% in DZ twin pairs, the difference was statistically significant (P<0.001). The concordance rate of type 2 diabetes in MZ twin parts was higher than that in DZ twin pairs in both men and women, in different age groups and in different areas (P<0.05). Further stratified analysis showed that in northern China, only MZ twin pairs less than 60 years old were found to have a higher concordance rate of type 2 diabetes compared with DZ twin pairs (P<0.05). In southern China, the co-prevalence rate in male MZ twin pairs aged ≥60 years was still higher than that in DZ twin pairs (P<0.05). Conclusion: The twin pairs in this study had a lower self-reported prevalence of type 2 diabetes than the general population. The study results suggested that genetic factors play a role in type 2 diabetes prevalence in both men and women, in different age groups and in different areas, however, the effect might vary.

[A descriptive analysis on coronary heart disease in adult twins in China].

Objective: To describe the distribution characteristics of coronary heart disease in adult twins recruited from Chinese Twin Registry (CNTR), and provide clues and evidence for the effect of genetic and environmental influences on coronary heart disease. Methods: By using the data of CNTR during 2010-2018, a total of 34 583 twin pairs aged ≥18 years who completed questionnaire survey and had related information were included in the current study to analyze the population and area distribution characteristics of coronary heart disease. Random effect models were used to compare the differences between groups. The concordane rate of coronary heart disease were calculated respectively in monozygotic (MZ) twin pairs and dizygotic (DZ) twin pairs to estimate the heritability. Results: The twin pairs included in this analysis were aged (34.2±12.4) years. The overall prevalence rate of coronary heart disease in twin pairs was 0.7%. Twin pairs who were women, older, obese and lived in northern China had higher prevalence of coronary heart disease (P<0.05). Intra-pair analysis in the same-sex twin pairs found that the concordane rate of coronary heart disease was higher in MZ twin pairs (25.3%) than in DZ twins (7.4%), and the difference was statistically significant (P<0.001). The overall heritability of coronary heart disease was 19.3% (95%CI: 11.8%-26.8%). Stratified by gender, age and area, the concordane rate was still higher in MZ twin pairs than in DZ pairs. Participants who were women, aged 18-30 years or ≥60 years and lived in northern China had a higher heritability of coronary heart disease. Conclusion: The distribution of coronary heart disease in twin pairs differed in populations and areas. The prevalence of coronary heart disease was affected by genetic factors, but the effect varied with age, gender and area.

Mitochondrial quality control in cartilage damage and osteoarthritis: new insights and potential therapeutic targets.

Osteoarthritis (OA) is a multifactorial arthritic disease of weight-bearing joints concomitant with chronic and intolerable pain, loss of locomotion and impaired quality of life in the elderly population. Although the prevalence of OA increases with age, its specific mechanisms have not been elucidated and effective therapeutic disease-modifying drugs have not been developed. As essential organelles in chondrocytes, mitochondria supply energy and play vital roles in cellular metabolism, proliferation and apoptosis. Mitochondrial quality control (MQC) is the key mechanism to coordinate various mitochondrial biofunctions, primarily through mitochondrial biogenesis, dynamics, autophagy and the newly discovered mitocytosis. An increasing number of studies have revealed that a loss of MQC homeostasis contributes to the cartilage damage during the occurrence and development of OA. Several master MQC-associated signaling pathways and regulators exert chondroprotective roles in OA, while cartilage damage-related molecular mechanisms have been partially identified. In this review, we summarized known mechanisms mediated by dysregulated MQC in the pathogenesis of OA and latent bioactive ingredients and drugs for the prevention and treatment of OA through the maintenance of MQC.

Prospective Associations between Plasma Amyloid-Beta 42/40 and Frailty in Community-Dwelling Older Adults.

BACKGROUND: Brain amyloid-beta (Aß) plaques, a hallmark of the pathophysiology of Alzheimer's disease, have been associated with frailty. Whether the plasma Aß markers show similar relationship with frailty is unknown. OBJECTIVES: To investigate the prospective associations between plasma Aß42/40 ratio and overtime frailty in community-dwelling older adults. METHODS: From the 5-year Multidomain Alzheimer Preventive Trial (MAPT), we included 477 adults ≥70 years with available data on plasma Aß42/40 ratio (lower is worse). Fried frailty phenotype (robust, pre-frail and frail) was assessed at the same time-point of plasma Aß measures and after until the end of follow-up. The outcomes of interest were the change in the frailty phenotype over time (examined by mixed-effect ordinal logistic regressions) and incident frailty (examined by Cox proportional hazard models). RESULTS: Plasma Aß42/40 did not show significant associations with incident frailty; however, after adjusting for Apolipoprotein E (APOE) ε4 genotype, people in the lower quartile of plasma Aß42/40 (≤0.103) had higher risk of incident frailty (HR=2.63; 95% CI, 1.00 to 6.89), compared to those in the upper quartile (>0.123). Exploratory analysis found a significant association between the lower quartile of plasma Aß42/40 and incident frailty among APOE ε4 non-carriers (HR=3.48; 95% CI, 1.19 to 10.16), but not among carriers. No associations between plasma Aß42/40 and evolution of frailty were observed. CONCLUSION: No significant associations between plasma Aß42/40 and frailty were found when APOE ε4 status was not accounted into the model. Nevertheless, APOE ε4 non-carriers with high Aß burden might be more susceptible to develop frailty.

Can We Distinguish Age-Related Frailty from Frailty Related to Diseases ? Data from the MAPT Study.

BACKGROUND: No study has tried to distinguish subjects that become frail due to diseases (frailty related to diseases) or in the absence of specific medical events; in this latter case, it is possible that aging process would act as the main frailty driver (age-related frailty). OBJECTIVES: To classify subjects according to the origin of physical frailty: age-related frailty, frailty related to diseases, frailty of uncertain origin, and to compare their clinical characteristics. MATERIALS AND METHODS: We performed a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT), including 195 subjects ≥70 years non-frail at baseline who became frail during a 5-year follow-up (mean age 77.8 years ± 4.7; 70% female). Physical frailty was defined as presenting ≥3 of the 5 Fried criteria: weight loss, exhaustion, weakness, slowness, low physical activity. Clinical files were independently reviewed by two different clinicians using a standardized assessment method in order to classify subjects as: "age-related frailty", "frailty related to diseases" or "frailty of uncertain origin". Inconsistencies among the two raters and cases of uncertain frailty were further assessed by two other experienced clinicians. RESULTS: From the 195 included subjects, 82 (42%) were classified as age-related frailty, 53 (27%) as frailty related to diseases, and 60 (31%) as frailty of uncertain origin. Patients who became frail due to diseases did not differ from the others groups in terms of functional, cognitive, psychological status and age at baseline, however they presented a higher burden of comorbidity as measured by the Cumulative Illness Rating Scale (CIRS) (8.20 ± 2.69; vs 6.22 ± 2.02 frailty of uncertain origin; vs. 3.25 ± 1.65 age-related frailty). Time to incident frailty (23.4 months ± 12.1 vs. 39.2 ± 19.3 months) and time spent in a pre-frailty condition (17.1 ± 11.4 vs 26.6 ± 16.6 months) were shorter in the group of frailty related to diseases compared to age-related frailty. Orthopedic diseases (n=14, 26%) were the most common pathologies leading to frailty related to diseases, followed by cardiovascular diseases (n=9, 17%) and neurological diseases (n = 8, 15%). CONCLUSION: People classified as age-related frailty and frailty related to diseases presented different frailty-associated indicators. Future research should target the underlying biological cascades leading to these two frailty classifications, since they could ask for distinct strategies of prevention and management.

[The predictive value of ultrasonic measurement of the diaphragmatic thickening fraction combined with the maximal inspiratory pressure in mechanical ventilation patients].

Objective: To evaluate the value of the diaphragmatic thickening fraction (DTF) combined with the maximum inspiratory pressure (MIP) for the prediction of weaning success in mechanically ventilated patients. Methods: Patients admitted to the intensive care unit (ICU) of Yijishan Hospital of Wannan Medical College and on mechanical ventilation for 24 hours from June 2018 to April 2019 were selected as the study subjects. A low-level pressure support ventilation (PSV) method was applied to conduct a spontaneous breathing test (SBT) for 30 minutes after the patients met the screening conditions for clinical weaning; and the patients were weaned when they met the clinical weaning criteria. Before weaning, the patient's MIP was measured. The right hemidiaphragmatic excursion (DE) and the thickness of the diaphragm at the end of inspiration and at the end of exhalation were measured by ultrasound, and the DTF was calculated. The statistical relationship between the DTF, DE and MIP was analyzed. The predictive value for the success of weaning was calculated with the DTF, DE and MIP and was evaluated by the area under the receiver operating characteristic curve (AUC). Results: A total of 73 patients were included in this study, including 57 patients who were successfully weaned, and 16 patients who experienced failure. The DTF of the successful weaning group (35%, 8%) was significantly higher than that of the failed weaning group (25%±5%), and the difference was statistically significant (t=6.401, P<0.01). The MIP (34±9 cmH(2)O) in the successful weaning group was significantly higher than that in the failed weaning group (23±3 cmH(2)O), and the difference was statistically significant (t=7.186, P<0.01). The ROCs for the DTF, MIP, and diaphragmatic displacement were 0.907, 0.896, and 0.749, respectively. A DTF ≥ 27.78%, with a sensitivity of 92.98%, a specificity of 81.25%, and an AUC of 0.907 (95% CI: 0.816-0.963), was used as the standard to predict the success of weaning. An MIP>26.5 cmH(2)O, with a sensitivity of 80.7%, a specificity of 93.75%, and an AUC of 0.896 (95% CI: 0.803-0.955), was used as the standard to predict the success of weaning. The AUC of DTF ≥ 27.78% and MIP ≥ 26.5 cmH(2)O was 0.920 (95% CI:0.832-0.971), and the specificity increased to 87.7%, but the sensitivity was slightly reduced to 87.5%. Conclusions: The DTF and MIP play a crucial role in determining the appropriate time and predicting the outcome of weaning of mechanical ventilation patients. Compared with the DTF and MIP alone, the DTF combined with MIP greatly improved the accuracy of predicting successful weaning.

Distortion and magnification of four digital cephalometric units.

OBJECTIVES: To assess the validity of using the calibration ruler for correcting magnification of linear measurements and to explore and compare the vertical and horizontal magnification of four digital cephalometric units. METHODS: An acrylic box was imaged at seven sagittal positions using four digital cephalometric units: Orthopantomograph OC100, Orthopantomograph OC200, Sirona Orthophos CD, and Sirona Orthophos DS. The true linear lengths of the phantom, corrected, and uncorrected linear lengths on the images were measured and compared. The validity of measurements using the calibration ruler was assessed. The magnification values and distortion indices were calculated and compared among the four cephalometric units. RESULTS: For linear measurements on the mid-sagittal plane and averaged linear measurements on bilateral symmetric sagittal planes, the bias 1.96 STD of the calibration ruler ranged from 1% to 2% for the four cephalometric testing units. For linear measurements on the single lateral sagittal plane, the bias 1.96 STD ranged from 3% to 6%. The vertical scanning charge-coupled device cephalometric unit produced the greatest distortion, ranging from 1.029 to 0.964. CONCLUSION: The metal millimeter calibration ruler is an accurate reference for linear measurement magnification correction. Because of unpredictability and machine specificity, the magnification and distortion of a cephalometric unit should be calibrated for the estimation of cephalometric measurement error.

PM2.5 stimulated the release of cytokines from BEAS-2B cells through activation of IKK/NF-κB pathway.

Previous studies indicated that exposure to fine particulate matter (PM2.5) was related to pulmonary inflammatory diseases through activation of nuclear factor kappa B (NF-κB) signaling pathway to trigger cytokine secretions in human lung carcinoma cells. To investigate the potential mechanisms underlying expression of cytokines via activated NF-κB by PM2.5, human bronchial epithelial cells (BEAS-2B cells) were treated with PM2.5 extracts at different concentrations (6, 13, 25, 50, 100, 200, and 400 µg mL-1) for 6 and 24 h. We found that 100 µg mL-1 PM2.5 increased interleukin 6 (IL-6) and IL-8 expression at 24 h (p < 0.05 or p < 0.01). Moreover, 100 µg mL-1 PM2.5 upregulated phosphorylated IκB kinase (IKK), p65, and IκBα at 6 h, which could be reversed by the IKK inhibitor Bay11-7082 (p < 0.05 or p < 0.01). The p65 subunit of NF-κB was translocated into the nucleus of the cells treated with 100 µg mL-1 PM2.5 at 6 and 24 h. Bay11-7082 partly inhibited PM2.5-induced increases of IL-6 and IL-8 secretion. The results indicated that PM2.5 extract increased IL-6 and IL-8 levels in BEAS-2B cells through activation of IKK/NF-κB pathway. Our study will contribute to better understanding of the mechanism of PM2.5-induced pulmonary inflammatory diseases.

Clinical Impact of Stent Implantation for Coarctation of the Aorta with Associated Hypoplasia of the Transverse Aortic Arch.

The aim of this study was to explore the clinical impact of transverse aortic arch hypoplasia (TAH) after stent implementation for isthmal coarctation of the aorta (CoA). From a retrospective chart review, 51 children (median age 11.1 years) were identified who had TAH and a CoA stent implanted between 10/1995 and 4/2015. Arm-leg cuff blood pressure measurements, echocardiographic arch imaging, and 24-h ambulatory blood pressure monitoring, prior to and after stent implantation, were reviewed. At catheterization, peak systolic gradients across the CoA's were 25 mmHg before and 4 mmHg after stent implantation. At a median 37-month follow-up, echocardiographic imaging showed no significant catch-up growth in the transverse arch (median z-score; proximal and distal arch -1.54 and -1.99 vs. -1.78 and -1.63, p = 0.13 and 0.90). A trend to increasing systolic blood pressure (SBP) differentials between the right and left arms was noted (11 mmHg [prior to]; 16 mmHg [follow-up], p = 0.09). Age-adjusted percentiles for right arm SBP decreased from 99.7% prior to, and 87.6% in follow-up (p < 0.001). The median time to re-intervention was 5.6 years (95% CI [2.8, 7.8]) and the proportion of children using anti-hypertensive in follow-up was not significantly different before the implantation (38% [prior to]; 45% [follow-up]). Elevated right arm blood pressure persists after successful stent implantation in the setting of associated TAH and there appears to be no catch-up growth of the transverse arch with time. Medical management can be difficult and approaches to surgical arch augmentation or stent implantation should be considered to avoid unilateral arm hypertension.

ITD mutation in FLT3 tyrosine kinase promotes Warburg effect and renders therapeutic sensitivity to glycolytic inhibition.

Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity. Inhibition of glycolysis preferentially causes severe ATP depletion and massive cell death in FLT3/ITD leukemia cells. Glycolytic inhibitors significantly enhances the cytotoxicity induced by FLT3 tyrosine kinase inhibitor sorafenib. Importantly, such combination provides substantial therapeutic benefit in a murine model bearing FLT3/ITD leukemia. Our study suggests that FLT3/ITD mutation promotes Warburg effect, and such metabolic alteration can be exploited to develop effective therapeutic strategy for treatment of AML with FLT3/ITD mutation via metabolic intervention.

Nicotinamide Facilitates Mesenchymal Stem Cell Differentiation Into Insulin-Producing Cells and Homing to Pancreas in Diabetic Mice.

OBJECTIVE: This study aimed to investigate the effect of nicotinamide on differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) in vivo in mice and on homing of MSCs to the pancreas after being intravenously infused. METHODS: Streptozotocin (STZ)-induced diabetic Balb/c mice received syngeneic transplantation of carboxyfluorescein succinimidyl ester (CFSE)-labeled bone marrow MSCs into the liver or tail vein. Nicotinamide was intraperitoneally injected into mice at a dose of 500 mg/kg body weight per day after STZ administration. Mice who received saline solution injection instead of nicotinamide were involved as control. RESULTS: Mice that received nicotinamide injection showed lower blood glucose, higher serum insulin, and more improved glucose tolerance compared with the control group. Immunohistochemistry analysis showed that higher levels of insulin staining and higher percentages of CFSE+/insulin+ cells were observed in the liver and pancreas sections of mice who received nicotinamide injection compared with the control group. The percentage of CFSE+/insulin+ cells was positively correlated with serum insulin level. Real-time polymerase chain reaction results showed that the implanted MSCs in mice who received nicotinamide injection exhibited higher levels of ß-cell-related gene expression than the control group. More CFSE-labeled MSCs appeared in the pancreas of mice who received nicotinamide injection compared with the control group after being intravenously infused, whereas the amount of CFSE-labeled MSCs in the liver was not affected by nicotinamide injection. CONCLUSIONS: Nicotinamide facilitates MSCs differentiating into functional IPCs in vivo in diabetic mice and promotes intravenously infused MSCs to home to the pancreas.

Distinct non-cerebrovascular risk factors for ischemic lacunar stroke and non-lacunar stroke: preliminary results.

Stroke is a non-communicable disease of increasing socioeconomic importance in aging populations. This study compared the risk factors implicated in two subtypes of ischemic stroke: lacunar stroke (LS) and non-lacunar stroke (NLS). A retrospective case control study was conducted on a total of 368 patients [220 cases (59.8%) of NLS and 148 cases (40.2%) of LS] with first-time onset of ischemic stroke. Multivariate logistic regression was performed to compare multiple non-cerebrovascular risk factors between the two groups. More patients with a history of diabetes were found in the NLS than the LS group (40.5 vs 26.4%), and that both fasting glucose and HbA1C levels before the onset of stroke were higher in NLS than LS patients. Multivariate analysis revealed that patients with a history of diabetes were 1.57 times more likely to have NLS than LS (OR = 1.57, 95%CI = 0.95-3.26). Moreover, male patients were more likely to develop NLS than females (OR = 1.46, 95%CI = 0.79-2.69), and patients with elevated fibrinogen levels were 1.4 times more likely to develop NLS than LS (OR = 1.40, 95%CI = 1.09-1.80). Additionally, patients who were heavy drinkers (OR = 1.39, 95%CI = 0.68-2.84) or smokers (OR = 1.62, 95%CI = 0.91-2.89) were more likely to develop NLS than LS. Other risk factors, such as hypertension, dyslipidemia, age, and average blood pressure, did not differ between the two types of stroke. Thus, distinct non-cerebrovascular risk factors (male gender, long history of diabetes, elevated fibrinogen, heavy smoking, and heavy drinking) are associated with a higher risk of developing non-lacunar stroke than lacunar stroke.

Relationship between the TaqI B polymorphism of the cholesterol ester transfer protein gene and atrial fibrillation in Han and Kazak populations.

The TaqI B polymorphism in the cholesterol ester transfer protein (CETP) (B1 and B2 alleles; rs708272) is associated with changes in enzyme activity and lipid concentrations. The B1 allele of the CETP gene is a known independent risk factor for genetic susceptibility to atrial fibrillation (AF); however, little is known about this polymorphism in the minority groups of Xinjiang, China. We examined the role of this polymorphism in AF using two independent case-control studies: the Han population (101 AF patients and 129 control subjects) and the Kazak population (103 AF patients and 101 control subjects). Carriers of the B1B1 genotype were more frequent among AF patients than among controls both in the Han population (34.7 versus 26.4%; χ(2) = 10.686, P = 0.001) and in the Kazak population (53.4 versus 24.8%; χ(2) = 27.802, P < 0.001). The odds ratio (OR) for carriers of the B1B1 genotype to AF susceptibility was 0.187 [95% confidence interval (CI) = 0.071- 0.491] in the Han group and 8.426 (95%CI = 2.295-30.933) in the Kazak population. After adjustment of confounding factors such as gender, age, smoking, alcohol consumption, hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol, and high-density lipoprotein, the difference remained significant in the Han group (P = 0.001; OR = 0.187, 95%CI = 0.071-0.491) and in the Kazak group (P = 0.001; OR = 8.426, 95%CI = 2.295-30.933). The presence of the B1B1 polymorphism of the Taq1B CETP genotype contributes to the development of AF in the Han and Kazak populations in western China (Xinjiang).

Effect of pesticide 1-[6-chloro-3-methyl-pyridyl-8-nitro-7-methyl-1 2 3 5 6 7-hexahydro imidazo (1,2a)]-pyridine when responding to a wheat plant's antioxidant defense system.

The purpose of this research was to establish an analytical method for analysing the 1-[6-chloro-3-methyl-pyridyl-8-nitro-7-methyl-1 2 3 5 6 7-hexahydro imidazo-(1,2a)]-pyridine (IPP) residue levels and to evaluate the difference in plant growth and its physical condition. A high performance liquid chromatography connected to a diode array detector (HPLC-DAD) was also employed. The results showed that the content of protein and water soluble carbohydrate (WSC) treated by IPP were initially higher with a significant delayed decrease. The biomarker response showed, even at a lower dose rate, exposure to the IPP caused stress effects and modified the activity of superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT) and polyphenol oxidase (PPO). Different patterns of biomarker responses were observed by an increase in SOD and malondialdehyde (MDA), and differential effects for antioxidant enzymes with a decrease in CAT, POD and PPO. The conclusions show that this profile of biomarker variation could represent a useful method to characterise exposure to IPP in a wheat plant.

[Detection of residual antibiotics in honey with capillary electrophoresis].

Five antibiotics compounds, tetracycline (TC), oxytetracycline (OTC), doxycycline (DOC), chlortetracycline (CTC) and chloramphenicol (CP), were successfully separated and determined by high performance capillary electrophoresis(HPCE). Effects of buffer pH, various organic additives and temperature on electrophoretic separation of antibiotics were investigated. Satisfactory separation of these five antibiotics was achieved in the buffer of pH 3.2, 0.02 mol/L Na2HPO4-0.01 mol/L citric acid with addition of 4% (V/V) N-methylmorpholine and 12% (V/V) acetonitrile within 20 minutes. The calibration graphs were linear by plotting the peak area against the sample concentration over the range of 150 micrograms/L to 750 micrograms/L and the correlation coefficients were greater than 0.9917. The detection limits were 10 micrograms/L for CP, 20 micrograms/L for TC, OTC and DOC and 40 micrograms/L for CP (signal to noise ratio > 5). HPCE method was successfully applied to the analysis of trace antibiotics in honey.

[Preliminary studies on process and ultramicro-pulverization on pharmacodynamics of Leech].

OBJECTIVE: To compare pharmacodynamics of decoction and powder of Leech; To identify effect of pharmacodynamics of Leech with new methods of process and ultrmicro-pulverization. METHOD: The size of ultramicor-powder of Leech and new method processed Leech is determined by BT-1500 size distributive instrument. It is compared that the pharmacodynamics of Leech decoction and powder as well as ultramicro-powder with new method processed of 1/2 decoction dose by anticoagulation and antithrombus action of mice. The safety of different samples is identified. RESULT: The pharmacodynamics of samples is as ultramicro-powder of Leech with new method processed > ultrmicro-powder of Leech > powder of Leech > decoction of Leech. CONCLUSION: The ultramicro-powder of Leech with new method processed has better pharmacodynamic effect and the smell of Leech is improved.