Association of cumulative loneliness with all-cause mortality among middle-aged and older adults in the United States, 1996 to 2019.

Loneliness is a growing public health concern worldwide. We characterized the association between cumulative loneliness and subsequent all-cause mortality, using data from 9,032 participants aged 50+ in the population-based US Health and Retirement Study (HRS) from 1996 to 2019. Loneliness status (yes; no) was measured biennially from 1996 to 2004, and we categorized the experience of cumulative loneliness over the 8-y period as never, one time point, two time points, and ≥three time points. A multivariable-adjusted age-stratified Cox proportional hazards regression model was fitted to examine the association between cumulative loneliness from 1996 to 2004 and all-cause mortality from 2004 to 2019. Excess deaths due to each category of cumulative loneliness were calculated. Compared to those who never reported loneliness from 1996 to 2004, participants experiencing loneliness at one time point, two time points, and ≥three time points respectively had 1.05 (95% CI: 0.96 to 1.15), 1.06 (95% CI: 0.95 to 1.19), and 1.16 (95% CI: 1.02 to 1.33) times higher hazards of mortality from 2004 to 2019 (P trend = 0.01). These results correspond to 106 (95% CI: 68 to 144), 202 (95% CI: 146 to 259), and 288 (95% CI: 233 to 343) excess deaths per 10,000 person-years, for those experiencing loneliness at each of one, two, or ≥three time points from 1996 to 2004. Cumulative loneliness in mid-to-later life may thus be a mortality risk factor with a notable impact on excess mortality. Loneliness may be an important target for interventions to improve life expectancy in the United States.

Could differential under-reporting of loneliness between men and women bias the gender-specific association between loneliness duration and rate of memory decline? A probabilistic bias analysis of effect modification.

Gender is an observed effect modifier of the association between loneliness and memory aging. However, this effect modification may be a result of information bias due to differential loneliness under-reporting by gender. We applied probabilistic bias analyses to examine whether effect modification of the loneliness-memory decline relationship by gender is retained under three simulation scenarios with various magnitudes of differential loneliness under-reporting between men and women. Data were from biennial interviews with adults aged 50+ in the US Health and Retirement Study from 1996-2016 (5,646 women and 3,386 men). Loneliness status (yes vs. no) was measured from 1996-2004 using the CES-D loneliness item and memory was measured from 2004-2016. Simulated sensitivity and specificity of the loneliness measure were informed by a validation study using the UCLA Loneliness Scale as a gold standard. The likelihood of observing effect modification by gender was higher than 90% in all simulations, although the likelihood reduced with an increasing difference in magnitude of the loneliness under-reporting between men and women. The gender difference in loneliness under-reporting did not meaningfully affect the observed effect modification by gender in our simulations. Our simulation approach may be promising to quantify potential information bias in effect modification analyses.

Mid-Life Household Food Insecurity and Subsequent Memory Function and Rate of Decline in Rural South Africa, 2004-2022.

INTRODUCTION: We aimed to investigate mid-life food insecurity over time in relation to subsequent memory function and rate of decline in Agincourt, rural South Africa. METHODS: Data from the longitudinal Agincourt Health and Socio-Demographic Surveillance System (Agincourt HDSS) were linked to the population-representative Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI). Food insecurity (yes vs. no) and food insecurity intensity (never/rarely/sometimes vs. often/very often) in the past month were assessed every 3 years from 2004 to 2013 in Agincourt HDSS. Cumulative exposure to each food insecurity measure was operationalized as 0, 1, and ≥2 time points. Episodic memory was assessed from 2014/15 to 2021/22 in HAALSI. Mixed-effects linear regression models were fitted to investigate the associations of each food insecurity measure with memory function and rate of decline over time. RESULTS: A total of 3,186 participants (mean age [SD] in 2004: 53 [12.87]; range: 30-96) were included and 1,173 (36%) participants experienced food insecurity in 2004, while this figure decreased to 490 (15%) in 2007, 489 (15%) in 2010, and 150 (5%) in 2013. Experiencing food insecurity at one time point (vs. never) from 2004 to 2013 was associated with lower baseline memory function (ß = -0.095; 95% CI: -0.159 to -0.032) in 2014/15 but not rate of memory decline. Higher intensity of food insecurity at ≥2 time points (vs. never) was associated with lower baseline memory function (ß = -0.154, 95% CI: -0.338 to 0.028), although the estimate was imprecise. Other frequencies of food insecurity and food insecurity intensity were not associated with memory function or decline in the fully adjusted models. CONCLUSION: In this setting, mid-life food insecurity may be a risk factor for lower later-life memory function, but not decline.

Cumulative loneliness and subsequent memory function and rate of decline among adults aged ≥50 in the United States, 1996 to 2016

INTRODUCTION: The study objective was to investigate the association between loneliness duration and memory function over a 20-year period. METHODS: Data were from 9032 adults aged ≥50 in the Health and Retirement Study. Loneliness status (yes vs. no) was assessed biennially from 1996 to 2004 and its duration was categorized as never, 1 time point, 2 time points, and ≥3 time points. Episodic memory was assessed from 2004 to 2016 as a composite of immediate and delayed recall trials combined with proxy-reported memory. Mixed-effects linear regression models were fitted. RESULTS: A longer duration of loneliness was associated with lower memory scores (P < 0.001) and a faster rate of decline (P < 0.001). The association was stronger among adults aged ≥65 than those aged <65 (three-way interaction P = 0.013) and was stronger among women than men (three-way interaction P = 0.002). DISCUSSION: Cumulative loneliness may be a salient risk factor for accelerated memory aging, especially among women aged ≥65. HIGHLIGHT: A longer duration of loneliness was associated with accelerated memory aging. The association was stronger among women than men and among older adults than the younger. Reducing loneliness in mid- to late life may help maintain memory function.

Dissection of transcriptome dysregulation and immune characterization in women with germline BRCA1 mutation at single-cell resolution.

BACKGROUND: High-grade serous carcinoma (HGSC) is the most frequent and lethal type of ovarian cancer. It has been proposed that tubal secretory cells are the origin of ovarian HGSC in women with familial BRCA1/2 mutations. However, the molecular changes underlying malignant transformation remain unknown. METHOD: We performed single-cell RNA and T cell receptor sequencing of tubal fimbriated ends from 3 BRCA1 germline mutation carriers (BRCA1 carriers) and 3 normal controls with no high-risk history (non-BRCA1 carriers). RESULTS: Exploring the transcriptomes of 19,008 cells, predominantly from BRCA1+ samples, we identified 5 major cell populations in the fallopian tubal mucosae. The secretory cells of BRCA1+ samples had differentially expressed genes involved in tumor growth and regulation, chemokine signaling, and antigen presentation compared to the wild-type BRCA1 controls. There are several novel findings in this study. First, a subset of the fallopian tubal secretory cells from one BRCA1 carrier exhibited an epithelial-to-mesenchymal transition (EMT) phenotype, which was also present in the mucosal fibroblasts. Second, we identified a previously unreported phenotypic split of the EMT secretory cells with distinct evolutionary endpoints. Third, we observed increased clonal expansion among the CD8+ T cell population from BRCA1+ carriers. Among those clonally expanded CD8+ T cells, PD-1 was significantly increased in tubal mucosae of BRCA1+ patients compared with that of normal controls, indicating that T cell exhaustion may occur before the development of any premalignant or malignant lesions. CONCLUSION: These results indicate that EMT and immune evasion in normal-looking tubal mucosae may represent early events leading to the development of HGSC in women with BRCA1 germline mutation. Our findings provide a probable molecular mechanism explaining why some, but not all, women with BRCA1 germline mutation present with early development and rapid dissemination of HGSC.

Trends and geographic variations in self-reported diabetes incidence: A prospective open cohort study of Chinese men and women, 1997-2015.

AIM: This study aims to evaluate the trends and geographic variations of incident diabetes as well as the corresponding sex differences in China. METHODS: The open cohort study derived data of 16,610 individuals from the China Health and Nutrition Survey 1997-2015. Direct standardisation was employed to calculate the age-standardised diabetes incidence. Mixed effects logistic regression models with interaction terms were performed to examine variations in incident diabetes. Socio-demographic (age, sex, marital status, racial compositions and educational attainment) and lifestyle attributes (smoking history, BMI and waist circumference) were sequentially included as covariates. RESULTS: Overall age-standardised diabetes incidence increased from 2.94 per 1000 person-years (95% CI, 2.44-3.44) in 1997-2004 to 5.54 (95% CI, 4.94-6.14) in 2009-2015. Models with interaction terms suggest that the increase among men was higher than that among women (wave 2006-2009 × Female: OR = 0.45, 95% CI 0.28-0.72). Age-standardised incidence of diabetes varied across regions, ranging from 5.67 (95% CI, 4.95-6.40) in Eastern China to 2.69 (95% CI 2.19-3.19) in Western China. Subsequent modelling analyses suggest that the geographic variations could be mostly explained by the variations in the BMI and waist circumference across regions. CONCLUSIONS: Results suggest that the incidence of self-reported diabetes approximately doubled during the study period. The increase among men was steeper than that among women. Public interventions reducing the population's obesity level hold promise to alleviate geographic variations and flatten the growth curve.

Physician distribution across China's cities: regional variations.

BACKGROUND: Distribution of physicians is a key component of access to health care. Although there is extensive research on urban-rural disparities in physician distribution, limited attention has been directed to the heterogeneity across urban areas. This research depicts variations in physician density across over 600 cities in the context of China's rapid urbanization. METHODS: Data came from National Census Surveys and China statistical yearbooks, 2000-2003, and 2010-2013. Cities were characterized in terms of not only administrative level but also geographic regions and urban agglomerations. We analyzed variations in physician supply by applying generalized estimating equations with an ordinal logistic linking function. RESULTS: Although overall physician density increased between 2003 and 2013, with population and socioeconomic attributes adjusted, physician density declined in urban China. On average, urban districts had a higher physician density than county-level cities, but there were regional variations. Cities in urban agglomerations and those outsides did not differ in physician density. CONCLUSION: Despite the reduced inequality between 2003 and 2013, the growth in physician density did not appear to be commensurate with the changes in population health demand. Assessment in physician distribution needs to take into account heterogeneity in population and socioeconomic characteristics.

All-cause mortality rate in China: do residents in economically developed regions have better health?

BACKGROUND: Urban-rural disparities have been extensively investigated, while most investigators overlooked urban-suburban-rural variations in population health. Although regional disparities in East-West China have been largely discussed, limited attention has been directed to the interaction between regional differences and urban-suburban-rural disparities. This study aims to analyze urban-suburban-rural variations in all-cause mortality rates across four geographic regions in China. METHODS: Data came from China's National Census Survey and public statistical yearbooks in 2000 and 2010. Urban districts, county-level cities, and counties were respectively defined as urban, suburban, and rural areas. We obtained 2322 areas, including 2148 areas with two observations and 174 areas with only one observation. Data visualization was performed to depict geographic variations and changes in all-cause mortality rates. Five hierarchical linear regression analyses with generalized estimating equations (GEE) were employed to analyze variations in all-cause mortality rates over time. Demographic and socioeconomic attributes were introduced as covariates. RESULTS: Despite an overall decline in all-cause mortality rate, rural residents generally achieved worse health than urban and suburban counterparts. In contrast, urban-suburban disparities could be fully explained by demographic and socioeconomic differences. In addition, Northeastern and Central residents achieved better health than Eastern and Western residents. Last, there existed urban/suburban-rural disparities in all regions, except Northeastern, where urban/suburban-rural disparities were eliminated after controlling for socioeconomic and demographic attributes. CONCLUSION: Even though suburban and rural areas were often merged, there exist urban/suburban-rural disparities in population health. Furthermore, urban/suburban-rural disparities vary across regions.

Neighborhood's locality, road types, and residents' multimorbidity: evidence from China's middle-aged and older adults.

BACKGROUND: Neighborhood factors have gained increasing attention, while the association between the neighborhood's characteristics and multimorbidity has not been clarified. In this study, we aim to depict variations in the number of non-communicable chronic diseases (NCDs) as a function of urban vs. rural settings and road types. METHODS: The present cross-sectional study derived data from the China Health and Retirement Longitudinal Study 2011 National Baseline Survey. Negative binomial regression with clustered robust standard errors was performed to analyze variations in the number of NCDs among 13,414 Chinese middle-aged and older adults. Logistic regression models were employed to investigate the association between neighborhood-level characteristics and each NCD, respectively. RESULTS: First, over 65% of subjects had at least one NCDs, and over 35% had multimorbidity. Arthritis (33.08%), hypertension (24.54%), and digestive disease (21.98%) were the most prevalent NCDs. Urban vs. rural differences in multimorbidity were fully explained by neighborhood clustering variations (IRR = 1.02, 95% CI, 0.95-1.10). Living with paved roads was associated with a smaller number of NCDs relative to living with unpaved roads (IRR = 0.86, 95% CI, 0.78-0.95). Results from subgroup analyses suggested that in comparison with those living with unpaved roads, individuals living with paved roads respectively had lower odds of chronic lung disease (OR = 0.76, 95% CI, 0.63-0.93), chronic liver disease (OR = 0.74, 95% CI, 0.55-0.99), chronic kidney disease (OR = 0.68, 95% CI, 0.51-0.89), digestive disease (OR = 0.82, 95% CI, 0.69-0.97), arthritis or rheumatism (OR = 0.69, 95% CI, 0.55-0.87), and asthma (OR = 0.67, 95% CI, 0.51-0.88). CONCLUSIONS: Urban vs. rural disparities in multimorbidity appeared to result from within-neighborhoods characteristics. The improvement in neighborhood-level characteristics, such as road pavement, holds promise to alleviate the increasing disease burden of chronic diseases.

Correction to: Neighborhood's locality, road types, and residents' multimorbidity: evidence from China's middle-aged and older adults.

An amendment to this paper has been published and can be accessed via the original article.

Health variations among breast-cancer patients from different disease states: evidence from China.

BACKGROUND: This study aimed to obtain health utility parameters among Chinese breast cancer patients in different disease states for subsequent health economics model. In addition, we aimed to explore the feasibility of establishing a breast cancer health utility mapping model in China. METHODS: Multiple patient-reported health attributes were assessed, including quality of life, which was measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument; health utility and self-rated health, which were measured by the EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire. Multivariate regression models, including a linear regression model, an ordinal logistic regression model and a Tobit model, were employed to analyze health differences among 446 breast cancer patients. Subgroup analyses were performed to examine differences in multiple dimensions of health derived from the FACT-B and EQ-5D-5L instruments. A mapping function was used to estimate health utility from quality of life. Rank correlation analyses were employed to examine the correlation between estimated and observed health utility values. RESULTS: A total of 446 breast cancer patients with different disease states were analyzed. The health utility values of breast cancer patients in the P state (without cancer recurrence and metastasis), R state (with cancer recurrence within a year), S state (with primary and recurrent breast cancer for the second year and above), and M state (metastatic cancer) were 0.81 (SD ± 0.23), 0.90 (SD ± 0.12), 0.78 (SD ± 0.31), and 0.74 (SD ± 0.27), respectively. There were positive correlations between all scores, including every domain of the FACT-B instrument (p < 0.001). Results from multivariate analysis suggested that patients in the R and M states had lower scores for overall quality of life (R, ß = - 9.45, p < 0.01; M, ß = - 6.72, p < 0.05). Patients in the M state had lower health utility values than patients in the P state (ß = - 0.11, p < 0.05). Estimated health utility values, which were derived from quality of life by using a mapping function, were significantly correlated with directly measured health utility values (p < 0.001). CONCLUSIONS: We obtained the health utility and health-related quality of life (HRQoL) scores of Chinese breast cancer patients in different disease states. Mapping health utility values from quality of life using four disease states could be feasible in health economic modelling, but the mapping function may need further revision.

Patients' Perceptions of Barriers and Facilitators to the Adoption of E-Hospitals: Cross-Sectional Study in Western China.

BACKGROUND: As an innovative approach to providing web-based health care services from physical hospitals to patients at a distance, e-hospitals (ie, extended care hospitals through the internet) have been extensively developed in China. This closed health care delivery chain was developed by combining e-hospitals with physical hospitals; treatment begins with web-based consultation and registration, and then, patients are diagnosed and treated in a physical hospital. This approach is promising in its ability to improve accessibility, efficiency, and quality of health care. However, there is limited research on end users' acceptance of e-hospitals and the effectiveness of strategies aimed to prompt the adoption of e-hospitals in China. OBJECTIVE: This study aimed to provide insights regarding the adoption of e-hospitals by investigating patients' willingness to use e-hospitals and analyzing the barriers and facilitators to the adoption of this technology. METHODS: We used a pretested self-administered questionnaire and performed a cross-sectional analysis in 1032 patients across three hierarchical hospitals in West China from June to August 2019. Patients' sociodemographic characteristics, medical history, current disease status, proficiency with electronic devices, previous experience with web-based health services, willingness to use e-hospitals, and perceived facilitators and barriers were surveyed. Multiple significance tests were employed to examine disparities across four age groups, as well as those between patients who were willing to use e-hospitals and those who were not. Multivariate logistic regression was also performed to identify the potential predictors of willingness to use e-hospitals. RESULTS: Overall, it was found that 65.6% (677/1032) of participants were willing to use e-hospitals. The significant predictors of willingness to use e-hospitals were employment status (P=.02), living with children (P<.001), education level (P=.046), information technology skills (P<.001), and prior experience with web-based health care services (P<.001), whereas age, income, medical insurance, and familiarity with e-hospitals were not predictors. Additionally, the prominent facilitators of e-hospitals were convenience (641/677, 94.7%) and accessibility to skilled medical experts (489/677, 72.2%). The most frequently perceived barrier varied among age groups; seniors most often reported their inability to operate technological devices as a barrier (144/166, 86.7%), whereas young participants most often reported that they avoided e-hospital services because they were accustomed to face-to-face consultation (39/52, 75%). CONCLUSIONS: We identified the variables, facilitators, and barriers that play essential roles in the adoption of e-hospitals. Based on our findings, we suggest that efforts to increase the adoption of e-hospitals should focus on making target populations accustomed to web-based health care services while maximizing ease of use and providing assistance for technological inquiries.

Accurate prediction and elucidation of drug resistance based on the robust and reproducible chemoresponse communities.

Selecting the available treatment for each cancer patient from genomic context is a core goal of precision medicine, but innovative approaches with mechanism interpretation and improved performance are still highly needed. Through utilizing in vitro chemotherapy response data coupled with gene and miRNA expression profiles, we applied a network-based approach that identified markers not as individual molecules but as functional groups extracted from the integrated transcription factor and miRNA regulatory network. Based on the identified chemoresponse communities, the predictors of drug resistance achieved high accuracy in cross-validation and were more robust and reproducible than conventional single-molecule markers. Meanwhile, as candidate communities not only enriched abundant cellular process but also covered a variety of drug enzymes, transporters, and targets, these resulting chemoresponse communities furnished novel models to interpret multiple kinds of potential regulatory mechanism, such as dysregulation of cancer cell apoptosis or disturbance of drug metabolism. Moreover, compounds were linked based on the enrichment of their common chemoresponse communities to uncover undetected response patterns and possible multidrug resistance phenotype. Finally, an omnibus repository named ChemoCommunity (http://www.jianglab.cn/ChemoCommunity/) was constructed, which furnished a user-friendly interface for a convenient retrieval of the detailed information on chemoresponse communities. Taken together, our method, and the accompanying database, improved the performance of classifiers for drug resistance and provided novel model to uncover the possible regulatory mechanism of individual response to drug.

Proliferation genes in lung development associated with the prognosis of lung adenocarcinoma but not squamous cell carcinoma.

There are many similarities between embryonic development and tumorigenesis, and gene expression profiles show that certain correlations exist between the gene signature during development and the clinical phenotypes of different cancers. Our group previously reported the gene expression profiles of human lung development, and the expression of one group of proliferation-related genes (PTN1 genes) steadily decreased during lung development. Here, we examined the prognostic value of PTN1 genes in 5 independent lung adenocarcinoma (ADC) and 5 lung independent squamous cell carcinoma (SCC) microarray datasets and found that the expression levels of PTN1 genes were associated with survival in lung ADC but not lung SCC. All of the lung ADC datasets contained a set of highly correlated genes from PTN1 genes, but the lung SCC datasets had no similar set of genes. We identified 63 unique core genes from the PTN1 genes in the 5 lung ADC datasets: 17 of these core genes appeared in at least 4 of the lung ADC datasets, and the 17 corresponding proteins clearly interacted more strongly with each other in lung ADC than in lung SCC. Moreover, 16 of the 17 core genes play major roles in the G2 /M phase of the cell cycle. These data indicate that proliferation-related genes in lung development have a significant prognostic value for lung ADC; the synergistic effects of the 17 core genes play an important role in lung ADC prognosis. These genes may have significant clinical implications for the treatment and prognosis of lung ADC.

[Comparison analysis of muscle enzymes in children with myocarditis and Duchene/Becker muscular dystrophy].

OBJECTIVE: To compare the changes in muscle enzyme between children with myocarditis and Duchene/Becker muscular dystrophy (DMD/BMD), and to seek the explanations for variation.
 METHODS: The retrospective analysis for 83 myocarditis children (myocarditis group) and 69 DMD/BMD children (DMD/BMD group), who were collected from Department of Pediatric of Shengjing Hospital affiliated to China Medical University since January 2008 to May 2015, was carried out. At the same time, 24 healthy children from the Department of Pediatric Development served as a control group. The examination indexes included creatine kinase (CK), creatine kinase-isoenzyme MB (CK-MB), creatine kinase isoenzyme MB mass (CK-MB mass), cardiac troponin I (cTnI) and high-sensitive-cTnT (hs-cTnT).
 RESULTS: 1) In the myocarditis group, the CK increased from 100 to 1 000 U/L, reached a peak after 5 days, which lasted for a week and then dropped to the normal; the CK-MB reached a peak after 5 to 7 days and dropped to the normal a month later; the CK-MB mass reached a peak on the first day and dropped to the normal after 3 weeks; the cTn reached to a peak after 5 days and dropped to the normal after about 17 days; hs-cTnT reached to a peak on the first day and dropped to the normal after about 19 days. 2) In the DMD/BMD group, the CK increased significantly and 27 cases had a CK value of more than 10 000 U/L. After the treatment for 1 to 2 weeks, their enzyme rose again after a slight drop. In terms of cTnI, 6 cases showed a moderate increase, 5 of them couldn't drop to the normal level until more than 3 weeks later; the hs-cTnT increased in the 45 cases, which lasted for more than 3 weeks in the 31 cases of them and showed a tendency of persisting increase.
 CONCLUSION: The cTnI and hs-cTnT rise significantly and possess wider observation window than CK and CK-MB mass in myocarditis children, with more sensitive and specific changes. The myocardial damage can occur before myasthenia and keep this trend for a long time in the DMD/BMD children. The trend of cTnI change in myocarditis children is similar to hs-cTnT, while hs-cTnT in DMD/BMD children is more sensitive than cTnI.

Exploring the genes associated with the response to intravenous immunoglobulin in patients with Kawasaki disease using DNA microarray analysis.

In this study we aimed to screen genes associated with intravenous immunoglobulin (IVIG) responding in patients with Kawasaki disease (KD) and thus explore the underlying molecular mechanism of IVIG resistance. The differentially expressed genes (DEGs) were identified by samr package in R. Then, protein-protein interaction (PPI) networks were constructed by STRING software. We further collected the regulatory data from TRANSFAC database, followed by regulatory interaction network construction. A total 194 of DEGs, including 185 up- and 9 down-regulated DEGs, were identified between IVIG-responding and non-responding patients with KD at acute stage. In contrast, no DEGs were found at convalescent stage. PPI networks and regulatory networks were constructed based on the 185 up-regulated genes at acute stage. The degrees of TFRC (transferrin receptor protein 1) and GADD45A (growth arrest and DNA-damage-inducible alpha) were higher than other genes, and meanwhile MYC (V-Myc Myelocytomatosis Viral Oncogene Homolog) and E2F1 (E2F Transcription Factor 1) were found to be two TFs (transcription factors) with the highest degrees. In conclusions, the response to IVIG in Kawasaki disease patients may be involved in the expression of TFRC, GADD45A, MYC and E2F1.

SM2miR: a database of the experimentally validated small molecules' effects on microRNA expression.

UNLABELLED: The inappropriate expression of microRNAs (miRNAs) is closely related with disease diagnosis, prognosis and therapy response. Recently, many studies have demonstrated that bioactive small molecules (or drugs) can regulate miRNA expression, which indicates that targeting miRNAs with small molecules is a new therapy for human diseases. In this study, we established the SM2miR database, which recorded 2925 relationships between 151 small molecules and 747 miRNAs in 17 species after manual curation from nearly 2000 articles. Each entry contains the detailed information about small molecules, miRNAs and evidences of their relationships, such as species, miRBase Accession number, DrugBank Accession number, PubChem Compound Identifier (CID), expression pattern of miRNA, experimental method, tissues or conditions for detection. SM2miR database has a user-friendly interface to retrieve by miRNA or small molecule. In addition, we offered a submission page. Thus, SM2miR provides a fairly comprehensive repository about the influences of small molecules on miRNA expression, which will promote the development of miRNA therapeutics. AVAILABILITY: SM2miR is freely available at http://bioinfo.hrbmu.edu.cn/SM2miR/.

Identification of active transcription factor and miRNA regulatory pathways in Alzheimer's disease.

MOTIVATION: Alzheimer's disease (AD) is a severe neurodegenerative disease of the central nervous system that may be caused by perturbation of regulatory pathways rather than the dysfunction of a single gene. However, the pathology of AD has yet to be fully elucidated. RESULTS: In this study, we systematically analyzed AD-related mRNA and miRNA expression profiles as well as curated transcription factor (TF) and miRNA regulation to identify active TF and miRNA regulatory pathways in AD. By mapping differentially expressed genes and miRNAs to the curated TF and miRNA regulatory network as active seed nodes, we obtained a potential active subnetwork in AD. Next, by using the breadth-first-search technique, potential active regulatory pathways, which are the regulatory cascade of TFs, miRNAs and their target genes, were identified. Finally, based on the known AD-related genes and miRNAs, the hypergeometric test was used to identify active pathways in AD. As a result, nine pathways were found to be significantly activated in AD. A comprehensive literature review revealed that eight out of nine genes and miRNAs in these active pathways were associated with AD. In addition, we inferred that the pathway hsa-miR-146a→STAT1→MYC, which is the source of all nine significantly active pathways, may play an important role in AD progression, which should be further validated by biological experiments. Thus, this study provides an effective approach to finding active TF and miRNA regulatory pathways in AD and can be easily applied to other complex diseases.

Meta-analysis of the relationship between single nucleotide polymorphism rs72689236 of caspase-3 and Kawasaki disease.

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology, for which a genetic influence is suspected. But whether single nucleotide polymorphism (SNP) of caspase-3 rs72689236 is associated with Kawasaki disease is controversial. The aim of our study is to assess the association between the SNP of caspase-3 and risk for Kawasaki disease. We searched PubMed, MEDLINE, EMBASE, Springer, Elsevier Science Direct, Cochrane Library Google scholar, CNKI (China National Knowledge Infrastructure, in Chinese) and Wanfang database (in Chinese) to identify studies investigating the association between rs72689236 polymorphism and Kawasaki disease occurrence. There were five eligible studies, which included 4,241 (case group 1,560; control group 2,681) participants in this meta-analysis. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated in a fixed-effects model (the Mantel-Haenszel method) or a random-effects model (the DerSimonian and Laird method) when appropriate. Significant associations were found under the overall ORs for A-allele comparison (A vs. G, pooled OR 1.33, 95 % CI 1.21-1.46), AA versus GG comparison (pooled OR 1.64, 95 % CI 1.35-2.00), GA versus GG comparison (pooled OR 1.42, 95 % CI 1.24-1.63), recessive model (AA vs. GG + GA, pooled OR 1.37, 95 % CI 1.15-1.64) and dominant model (AA + GA vs. GG, pooled OR 1.47, 95 % CI 1.29-1.67). This meta-analysis suggested that SNP rs72689236 of caspase-3 might be associated with susceptibility of Kawasaki disease and the allele A might increase the risk of Kawasaki disease in Asian samples such as Japanese and Chinese. In addition, individual studies with large sample size are needed to further evaluate the associations in various ethnic populations.

Quantifiable TCR repertoire changes in prediagnostic blood specimens among patients with high-grade ovarian cancer.

High-grade ovarian cancer (HGOC) is a major cause of death in women. Early detection of HGOC usually leads to a cure, yet it remains a clinical challenge with over 90% HGOCs diagnosed at advanced stages. This is mainly because conventional biomarkers are not sensitive enough to detect the microscopic yet metastatic early lesions. In this study, we sequence the blood T cell receptor (TCR) repertoires of 466 patients with ovarian cancer and controls and systematically investigate the immune repertoire signatures in HGOCs. We observe quantifiable changes of selected TCRs in HGOCs that are reproducible in multiple independent cohorts. Importantly, these changes are stronger during stage I. Using pre-diagnostic patient blood samples from the Nurses' Health Study, we confirm that HGOC signals can be detected in the blood TCR repertoire up to 4 years preceding conventional diagnosis. Our findings may provide the basis for future immune-based HGOC early detection criteria.