Optimization and application of pretreatment method of microplastics detection in municipal solid waste landfills.

The landfill is one of the most important sources of microplastics (MPs). The pretreatment method is a precondition of microplastics study for the presence of complex substances in landfills. Therefore, it is essential to examine the impact of different pretreatment methods on the microplastics detection. A literature review and a comparison experiment on digestion solutions were performed to establish a comprehensive identification method for MPs in landfills. When exposed to of 30 % H2O2, minimal mass reduction of PE, PP and PET were 4.00 %, 3.00 % and 3.00 % respectively, and the least surface damage was observed in MPs, while exhibiting the most optimal peak value for infrared spectral characteristics. It is demonstrated that the effect of 30 % H2O2 dissolution was superior compared to 10 % KOH and 65 % HNO3. The method was subsequently utilized to investigate the distribution of MPs in a landfill. The dominant MPs were polyethylene (PE, 18.56-23.91 %), polyethylene terephthalate (PET, 8.80-18.66 %), polystyrene (PS, 10.31-18.09 %), and polypropylene (PP, 11.60-14.91 %). The comprehensive identification method of "NaCl density separation + 30 % H2O2 digestion + NaI density separation + sampling microscope + Mirco-FTIR" is suitable for the detection of MPs in landfills.

Interaction between hypertension and frailty and their impact on death risk in older adults: a follow-up study.

BACKGROUND: Hypertension and frailty often occur concurrently, exhibiting increasing prevalence in the older population. In this study, we analyzed the frailty status among older adults with hypertension and the impact of their interaction on death risk. METHOD: This prospective cohort survey study included data from older people in an urban community in Beijing collected between 2009 and 2020 using the cluster random sampling method. The participants were older adults who were ≥ 60 years old at the time of investigation and had lived at the place of investigation for > 1 year. The survey variables comprised those related to health and frailty status assessed during the 2009 baseline survey, along with death-related information as outcome variables in 2020. Additionally, a frailty index (FI) model was used to examine the frailty status among the older adults at baseline. The effects of hypertension prevalence on the age-related frailty changes as well as on mortality for varying degrees of frailty were further analyzed. Lastly, Cox regression and Kaplan-Meier curves were applied to evaluate the impact of the interaction between hypertension and frailty on death risk. RESULTS: Ultimately, 1197 older individuals aged between 60 and 101 years(average age at baseline: 74.8 ± 8.6 years) were included .Among them, 475 individuals were men (mean age:74.8 ± 8.8 years), and 722 were women (mean age:74.8 ± 8.4 years).Frailty was identified in 151 individuals, leading to a prevalence rate of 12.6%(151/1197),while hypertension was detected in 593 (prevalence rate:49.5% [593/1197]).A total of 443 deaths were recorded by 2020, resulting in a mortality rate of 37.0% (443/1197).Moreover, FI values and mortality rates were higher at any age in older adults with hypertension compared with those without hypertension. Survival time analysis showed that the median survival time of older adults with hypertension and frailty was the shortest (39.0[95%CI: 35.6-42.3] months)when compared with that of older adults without hypertension but with frailty (52.9 [95%CI: 46.6-59.3] months), those with hypertension but without frailty (102.7 [95%CI: 98.7-106.8] months), and those without hypertension and frailty (127.9 [95%CI: 113.5-134.7] months),with log-rank x2 = 999.686 and P < 0.001. Furthermore, Cox regression results demonstrated that older adults with hypertension and frailty had the highest death risk when compared with that of older adults without hypertension and frailty (HR = 1.792, P < 0.001), those without hypertension but with frailty (HR = 1.484, P < 0.001), and those with hypertension but without frailty (HR = 1.406, P = 0.005). CONCLUSION: Frailty is prevalent among older adults with hypertension; however, older adults with both hypertension and frailty have a relatively higher mortality risk. Therefore, screening and assessment of frailty in the older population with hypertension are crucial for its early identification, thereby enabling timely and appropriate interventions to prevent or delay the adverse effects of this concurrent condition.

Clinical features and risk factors of lung cancer in elderly patients with dermatomyositis.

BACKGROUND: Although there are concerns about the association between dermatomyositis (DM) and malignancy, the clinical features in elderly DM patients with lung cancer are largely unknown. Here, we elucidated the clinical features and risk factors of lung cancer in elderly DM patients. METHODS: The data of elderly DM patients (≥65 years old) with or without lung cancer admitted to the Second Xiangya Hospital, Central South University from January 2016 to November 2022 were retrospectively analyzed. RESULTS: Male patients with elderly onset DM (EODM) symptoms were found to be prone to lung cancer (p < 0.001). Elderly DM patients with lung cancer had a higher ratio of a history of smoking and were more likely to present with heliotrope rash, V sign and dysphasia and elevated monocyte-to-lymphocyte ratio (MLR) and there was a higher ratio of anti-TIF1-γ-Ab-positive patients (all p < 0.05). Occurrence of interstitial lung disease (ILD), elevated aspartate aminotransferase (AST) and anti-aminoacyl-tRNA synthetase (anti-ARS)-antibody positive rates were less common in elderly DM patients with lung cancer than those without lung cancer (all p < 0.05). Multivariate logistic regression analysis showed smoking history (p = 0.011, OR = 4.532), elevated MLR (p = 0.018, OR = 1.159) and anti-TIF1-γ-Ab-positive status (p = 0.034, OR = 8.529) were independently associated with the presence of lung cancer, while ILD might be a protective factor (p = 0.024, OR = 0.179) for lung cancer in elderly patients with DM. CONCLUSIONS: Lung cancer is more common in male patients with EODM symptoms. Smoking, elevated MLR and being anti-TIF1-γ-Ab-positive were associated with higher frequencies of lung cancer in elderly DM patients. It is necessary to screen lung cancer in elderly DM patients with a history of smoking, elevated MLR or being anti-TIF1-γ-Ab-positive.

Chinese expert consensus on prevention and intervention for the elderly with malnutrition (2022).

Malnutrition is a state of altered body composition and body cell mass due to inadequate intake or utilization of energy or nutrients, leading to physical and mental dysfunction and impaired clinical outcomes. As one of the most common geriatric syndromes, malnutrition in the elderly is a significant risk factor for poor clinical outcomes, causing a massive burden on medical resources and society. The risk factors for malnutrition in the elderly are diverse and include demographics, chronic diseases, and psychosocial factors. Presently, recommendations for the prevention and intervention of malnutrition in the elderly are not clear or consistent in China. This consensus is based on the latest global evidence and multiregional clinical experience in China, which aims to standardize the prevention and intervention of malnutrition in the elderly in China and improve the efficacy of clinical practice and the prognosis of elderly patients.

Combined effect of diabetes and frailty on mortality among Chinese older adults: A follow-up study.

Background: Frailty and diabetes are two important health problems associated with aging in older individuals. This paper seeks to analyze the frailty in older adults suffering from diabetes and the combined effect of diabetes and frailty on mortality risk. Methods: The frailty index (FI) model was employed when evaluating frailty among the older adults based on the baseline data conducted in 2009; and death as outcome variables collected in 2020 were analyzed. The influence of diabetes on age-related changes in frailty in the older adults and resulting mortality rates was analyzed. Cox regression and Kaplan-Meier curves were applied to evaluate the influence on the risk of death and the 11-year survival of the older adults with varying diabetes and frailty statuses. Results: Ultimately, 1,213 older people aged between 60 and 101, with an average age of (74.79 ± 8.58) at baseline, were included in the analysis. By 2020, there had been 447 deaths with mortality at 36.9% (447/1,213); there were 271 cases of diabetes, with a prevalence of 22.3% (271/1,213). The mean FI value for older adults with diabetes was higher than that of those without regardless of age, and the average annual relative growth rate of the FI value for older adults with diabetes was higher than that of those without diabetes (ß = 0.039 vs. ß = 0.035, t = 8.367, P < 0.001). For all FI value levels, the mortality rate among older adults with diabetes was higher than that of those without. The Cox Regression analysis showed that, compared with those suffering from neither diabetes nor frailty, older adults with both had the higher mortality risk (HR = 1.760. P < 0.001), followed by older adults suffering from frailty alone (HR = 1.594, P = 0.006), and then by older adults suffering from only diabetes (HR = 1.475, P = 0.033). The survival analysis showed that the median survival of those suffering from diabetes and frailty to be the shortest at just 57.23 (95% CI: 54.05 to 60.41) months, lower than the 83.78 (95% CI: 79.33 to 88.23) months in those suffering from frailty alone, and 119.93 (95% CI: 113.84 to 126.02) months in those with only diabetes, and 124.39 (95% CI: 119.76 to 129.02) months in older adults with neither diabetes nor frailty (P < 0.001). Conclusion: Frailty is common among older adults suffering from diabetes, and there is an increased risk of poor health outcomes, such as death, among older adults suffering from diabetes and frailty. When diagnosing, treating, and dealing with older adults with diabetes, attention should be paid to screening and assessing frailty in hopes of identifying it early so that appropriate measures of intervention can be taken to avoid or delay the resulting adverse effects.

Frailty Status Among the Elderly of Different Genders and the Death Risk: A Follow-Up Study.

Background: Frailty in the elderly population is currently a frontier and focus in the field of health and aging. The goal of this study was to explore the frailty status among the elderly of different genders and its influence on the risk of death during 11 years. Methods: Frailty index (FI) was used to evaluate the frailty status in the elderly based on the baseline data conducted in 2009; and death as outcome variables collected in 2020 were analyzed. The difference of the frailty level and mortality of different genders was compared. Cox regression and Kaplan-Meier curves were applied to evaluate the influence on the risk of death and the 11-year survival of the elderly at different level of frailty, respectively. Results: Totally, 1,246 elderly people were recruited. The mortality in men (43.7%, 227/519) was statistically higher than that in women (34.3%, 249/727) (x 2 = 11.546, P = 0.001). Deficits accumulated exponentially with age, and at all ages, women accumulated more deficits than do men on average (B = 0.030 vs. 0.028, t = 4.137, P = 0.023). For any given level of frailty, the mortality rate is higher in men than in women, and the difference in mortality between genders reached the peak when FI value was 0.26. Cox regression analysis showed that FI value had a greater impact on the risk of death in older men (HR = 1.171, 95%CI: 1.139~1.249)than that in older women (HR = 1.119, 95%CI: 1.039~1.137). Survival analysis showed that the median 11-year survival time in women was longer than that in men (95.26 vs. 89.52 months, Log rank = 9.249, P = 0.002). Kaplan-Meier curves showed that the survival rate decreased with the increase of frailty, and at the same level of frailty, survival time in older women was longer than that in older men, except for severe frailty (FI ≥ 0.5). Conclusion: The frailty status and its influence on mortality are different among the older people of different genders; therefore, specific interventions for frailty should be conducted in the elderly population of different genders, as well as of different degrees of frailty.

Toward successful aging: The Chinese Health Criteria for the Elderly.

The Chinese Association of Geriatric Medicine proposed a set of criteria, The Health Criteria for the Elderly, to measure senior health. These criteria have their origins in the efforts in the past several decades to define successful aging. Successful aging theories, including the disengagement theory, the activity theory, and the continuity theory, represent sets of constructs on what elements constitute satisfactory aging and how it can be achieved. Rowe and Kahn's framework for successful aging emphasizes the impact of lifestyle choices on aging outcomes. The proposed health criteria for Chinese seniors may be too restrictive to be used as clinical guidelines. Instead, they can be promoted as goals of healthy aging in public education programs or serve as parameters to evaluate the effect of health policies and healthcare delivery models on the elderly population.

Diagnostic accuracy of intracellular mycobacterium tuberculosis detection for tuberculous meningitis.

RATIONALE: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity. OBJECTIVES: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis. METHODS: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6-expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients' final diagnosis. MEASUREMENTS AND MAIN RESULTS: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6-6.7%), compared with 82.9% (95% confidence interval, 77.4-87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8-80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4-93.8%) and 90.0% (95% confidence interval, 75.4-96.7%), respectively. CONCLUSIONS: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.

A robust method for genome-wide association meta-analysis with the application to circulating insulin-like growth factor I concentrations.

Genome-wide association studies (GWAS) offer an excellent opportunity to identify the genetic variants underlying complex human diseases. Successful utilization of this approach requires a large sample size to identify single nucleotide polymorphisms (SNPs) with subtle effects. Meta-analysis is a cost-efficient means to achieve large sample size by combining data from multiple independent GWAS; however, results from studies performed on different populations can be variable due to various reasons, including varied linkage equilibrium structures as well as gene-gene and gene-environment interactions. Nevertheless, one should expect effects of the SNP are more similar between similar populations than those between populations with quite different genetic and environmental backgrounds. Prior information on populations of GWAS is often not considered in current meta-analysis methods, rendering such analyses less optimal for the detecting association. This article describes a test that improves meta-analysis to incorporate variable heterogeneity among populations. The proposed method is remarkably simple in computation and hence can be performed in a rapid fashion in the setting of GWAS. Simulation results demonstrate the validity and higher power of the proposed method over conventional methods in the presence of heterogeneity. As a demonstration, we applied the test to real GWAS data to identify SNPs associated with circulating insulin-like growth factor I concentrations.

[Consequence and risk factors of falls-related injuries in community-dwelling elderly in Beijing].

OBJECTIVE: To investigate the incidence of falls during the past year,as well as the consequence of falls so as to explore the risk factors for fall-related injuries in the community-dwelling elderly in Beijing. METHODS: A cross-sectional study was conducted in a community in Beijing. A total of 1512 persons aged 60 years and over were selected using stratified cluster sampling method. Information related to all kinds of falls was collected with a standardized structured questionnaire through face-to-face interview. Binary logistic regression was used to explore the related factors for consequence of any falls, especially falls-related injuries in the elderly. RESULTS: 272 older adults had one falling episode at the baseline study, with the incidence rate of fall and the frequency of falls as 18.0% (272/1512) and 379 times respectively. Among the 1512 interviewees, 8.7% (131) suffered from injuries as a result of falls. Out of the total 379 times of falls, 143 resulted in injuries. Most common injuries appeared to be soft tissue related (84 times, 58.7%) and epidermal abrasion (57 times, 39.9%), followed by fracture (20 times, 14.0%) and open wound (9 times, 6.3%). The most common injured areas were lower limbs (67 times, 46.9%), followed by upper limbs (39 times, 27.3%), head (27 times, 18.9%), face (19 times, 13.3%), hip (11 times,2.9%), waist/abdomen (10 times, 2.6%), chest (6 times, 1.6%) ,vertebral column (5 times, 1.3%) and neck (3 times, 0.8%). Data from logistic regression analysis showed that being female (OR = 2.09), with proper bench height (OR = 1.94), being alcoholic (OR = 3.10), being able to walk more than 400 meters (OR = 2.11), fear of falls (OR = 3.30) etc. were risk factors, while enough handrails provided in surrounding areas (OR = 0.41) showed as the protective factor for falls-related injuries in the elderly. CONCLUSION: The incidence rates of falls and falls-related injuries among elderly community-dwellers in urban areas of Beijing were considered to be high. Falls and its related injuries were caused by varied factors, suggesting the intervention strategies should be targeted to the related factors as well as focusing on primary prevention.

[A prospective study on recurrent falls and related factors in elderly from the urban communities in Beijing].

OBJECTIVE: To investigate the incidence and risk factors for recurrent falls in community-dwelling elderly in Beijing. METHODS: A cross-sectional study was conducted in 472 elderly in the Longtan community of Dongcheng district,Beijing in 2009. Data on recurrent falls within the past 12 months were collected through face-to-face interview, with both single factor analysis and logistic regression analysis used to explore the related factors on recurrent falls in the elderly. RESULTS: The incidence of recurrent falls among 472 older adults was 6.1% (29) within the past 12 months. Results from logistic regression analysis showed that factors as higher family monthly income(OR = 1.39, 95% CI:0.67-2.16), afraid of being fallen(OR = 2.23, 95% CI:1.47-3.85)and abnormal static balance(OR = 2.48, 95% CI:1.84-4.05)were risk factors, while bench height in the surrounding environment(OR = 0.49, 95% CI:0.21-1.12)and easiness of access to daily supplies (OR = 0.41, 95%CI:0.14-1.16)were protective factors for recurrent falls. CONCLUSION: The incidence of recurrent falls among the elderly from the communities in Beijing was high. Since falls could be caused by various factors, intervention should be targeting on risk factors in a multi-dimensional way.

Genome-wide association study of clinical dimensions of schizophrenia: polygenic effect on disorganized symptoms.

OBJECTIVE: Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia. METHOD: Based on the Lifetime Dimensions of Psychosis Scale ratings of 2,454 case subjects of European ancestry from the Molecular Genetics of Schizophrenia (MGS) sample, three symptom factors (positive, negative/disorganized, and mood) were identified with exploratory factor analysis. Quantitative scores for each factor from a confirmatory factor analysis were analyzed for association with 696,491 single-nucleotide polymorphisms (SNPs) using linear regression, with correction for age, sex, clinical site, and ancestry. Polygenic score analysis was carried out to determine whether case and comparison subjects in 16 Psychiatric GWAS Consortium (PGC) schizophrenia samples (excluding MGS samples) differed in scores computed by weighting their genotypes by MGS association test results for each symptom factor. RESULTS: No genome-wide significant associations were observed between SNPs and factor scores. Most of the SNPs producing the strongest evidence for association were in or near genes involved in neurodevelopment, neuroprotection, or neurotransmission, including genes playing a role in Mendelian CNS diseases, but no statistically significant effect was observed for any defined gene pathway. Finally, polygenic scores based on MGS GWAS results for the negative/disorganized factor were significantly different between case and comparison subjects in the PGC data set; for MGS subjects, negative/disorganized factor scores were correlated with polygenic scores generated using case-control GWAS results from the other PGC samples. CONCLUSIONS: The polygenic signal that has been observed in cross-sample analyses of schizophrenia GWAS data sets could be in part related to genetic effects on negative and disorganized symptoms (i.e., core features of chronic schizophrenia).

An empirical Bayes mixture model for SNP detection in pooled sequencing data.

MOTIVATION: Detecting single-nucleotide polymorphism (SNP) in pooled sequencing data is more challenging than in individual sequencing because of sampling variations across pools. To effectively differentiate SNP signal from sequencing error, appropriate estimation of the sequencing error is necessary. In this article, we propose an empirical Bayes mixture (EBM) model for SNP detection and allele frequency estimation in pooled sequencing data. RESULTS: The proposed model reliably learns the error distribution by pooling information across pools and genomic positions. In addition, the proposed EBM model builds in characteristics unique to the pooled sequencing data, boosting the sensitivity of SNP detection. For large-scale inference in SNP detection, the EBM model provides a flexible and robust way for estimation and control of local false discovery rate. We demonstrate the performance of the proposed method through simulation studies and real data application. AVAILABILITY: Implementation of this method is available at https://sites.google.com/site/zhouby98.

Optimal methods for meta-analysis of genome-wide association studies.

Meta-analysis of genome-wide association studies involves testing single nucleotide polymorphisms (SNPs) using summary statistics that are weighted sums of site-specific score or Wald statistics. This approach avoids having to pool individual-level data. We describe the weights that maximize the power of the summary statistics. For small effect-sizes, any choice of weights yields summary Wald and score statistics with the same power, and the optimal weights are proportional to the square roots of the sites' Fisher information for the SNP's regression coefficient. When SNP effect size is constant across sites, the optimal summary Wald statistic is the well-known inverse-variance-weighted combination of estimated regression coefficients, divided by its standard deviation. We give simple approximations to the optimal weights for various phenotypes, and show that weights proportional to the square roots of study sizes are suboptimal for data from case-control studies with varying case-control ratios, for quantitative trait data when the trait variance differs across sites, for count data when the site-specific mean counts differ, and for survival data with different proportions of failing subjects. Simulations suggest that weights that accommodate intersite variation in imputation error give little power gain compared to those obtained ignoring imputation uncertainties. We note advantages to combining site-specific score statistics, and we show how they can be used to assess effect-size heterogeneity across sites. The utility of the summary score statistic is illustrated by application to a meta-analysis of schizophrenia data in which only site-specific P-values and directions of association are available.

MicroRNA programs in normal and aberrant stem and progenitor cells.

Emerging evidence suggests that microRNAs (miRNAs), an abundant class of ∼22-nucleotide small regulatory RNAs, play key roles in controlling the post-transcriptional genetic programs in stem and progenitor cells. Here we systematically examined miRNA expression profiles in various adult tissue-specific stem cells and their differentiated counterparts. These analyses revealed miRNA programs that are common or unique to blood, muscle, and neural stem cell populations and miRNA signatures that mark the transitions from self-renewing and quiescent stem cells to proliferative and differentiating progenitor cells. Moreover, we identified a stem/progenitor transition miRNA (SPT-miRNA) signature that predicts the effects of genetic perturbations, such as loss of PTEN and the Rb family, AML1-ETO9a expression, and MLL-AF10 transformation, on self-renewal and proliferation potentials of mutant stem/progenitor cells. We showed that some of the SPT-miRNAs control the self-renewal of embryonic stem cells and the reconstitution potential of hematopoietic stem cells (HSCs). Finally, we demonstrated that SPT-miRNAs coordinately regulate genes that are known to play roles in controlling HSC self-renewal, such as Hoxb6 and Hoxa4. Together, these analyses reveal the miRNA programs that may control key processes in normal and aberrant stem and progenitor cells, setting the foundations for dissecting post-transcriptional regulatory networks in stem cells.

Analysis of factorial time-course microarrays with application to a clinical study of burn injury.

Time-course microarray experiments are capable of capturing dynamic gene expression profiles. It is important to study how these dynamic profiles depend on the multiple factors that characterize the experimental condition under which the time course is observed. Analytic methods are needed to simultaneously handle the time course and factorial structure in the data. We developed a method to evaluate factor effects by pooling information across the time course while accounting for multiple testing and nonnormality of the microarray data. The method effectively extracts gene-specific response features and models their dependency on the experimental factors. Both longitudinal and cross-sectional time-course data can be handled by our approach. The method was used to analyze the impact of age on the temporal gene response to burn injury in a large-scale clinical study. Our analysis reveals that 21% of the genes responsive to burn are age-specific, among which expressions of mitochondria and immunoglobulin genes are differentially perturbed in pediatric and adult patients by burn injury. These new findings in the body's response to burn injury between children and adults support further investigations of therapeutic options targeting specific age groups. The methodology proposed here has been implemented in R package "TANOVA" and submitted to the Comprehensive R Archive Network at http://www.r-project.org/. It is also available for download at http://gluegrant1.stanford.edu/TANOVA/.

Hedgehog pathway-regulated gene networks in cerebellum development and tumorigenesis.

Many genes initially identified for their roles in cell fate determination or signaling during development can have a significant impact on tumorigenesis. In the developing cerebellum, Sonic hedgehog (Shh) stimulates the proliferation of granule neuron precursor cells (GNPs) by activating the Gli transcription factors. Inappropriate activation of Shh target genes results in unrestrained cell division and eventually medulloblastoma, the most common pediatric brain malignancy. We find dramatic differences in the gene networks that are directly driven by the Gli1 transcription factor in GNPs and medulloblastoma. Gli1 binding location analysis revealed hundreds of genomic loci bound by Gli1 in normal and cancer cells. Only one third of the genes bound by Gli1 in GNPs were also bound in tumor cells. Correlation with gene expression levels indicated that 116 genes were preferentially transcribed in tumors, whereas 132 genes were target genes in both GNPs and medulloblastoma. Quantitative PCR and in situ hybridization for some putative target genes support their direct regulation by Gli. The results indicate that transformation of normal GNPs into deadly tumor cells is accompanied by a distinct set of Gli-regulated genes and may provide candidates for targeted therapies.

Efficacy and safety of acarbose in the treatment of elderly patients with postprandial hypotension.

BACKGROUND: Postprandial hypotension (PPH) occurs frequently in elderly people and may lead to syncope, falls, dizziness, weakness, angina pectoris, and stroke. Some studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate at which glucose enters the small intestine. We hypothesized that acarbose (alpha-glucosidase inhibitor), a hypoglycemic agent that decreases the rate of glucose absorption in the small intestine, would attenuate PPH in the elderly, and would be safe in the treatment. METHODS: Forty-three elderly in-patients with PPH were recruited. All of them were in relatively stable conditions. They had semi-liquid standard meals without and with acarbose for the two following days: screening day and intervention day. Blood pressure and heart rate (HR) were recorded at baseline and every 15 minutes for 120 minutes using a non-invasive ambulatory blood pressure monitoring system during the study, and ejection fraction (EF) and fractional shortening (FS) were measured by two dimensional echocardiography. RESULTS: Compared with the screening day, the falls in systolic, diastolic and mean arterial blood pressure (SBP, DBP, MAP) (all P < 0.05) were significantly attenuated after taking acarbose during breakfast, so were MAP (P < 0.05) during lunch, DBP (P < 0.05) and MAP (P < 0.05) during supper. The change of HR was not statistically significant after taking acarbose in three meals. EF and FS were positively correlated with the relief rate. The effective power was 63%, and the incidence of adverse drug reaction (ADR) was 9%. CONCLUSION: Acarbose is effective and safe in the treatment of elderly patients with PPH.