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Background: The increasing prevalence of Alzheimer’s disease (AD), along with the associated burden on healthcare systems, presents a substantial public health challenge. Objective: This study aimed to investigate trends in AD mortality and the relevant burden across the United States (U.S.) from 1999 to 2018 and to predict mortality trends between 2019 and 2023. Methods: Data on AD-related deaths between 1999 and 2018 were collected from the WONDER database administered by the U.S. Centers for Disease Control and Prevention (CDC). The Joinpoint Regression Program was used to analyze mortality trends due to AD. Years of life lost (YLL) were calculated to explore the burden of AD deaths. An autoregressive integrated moving average (ARIMA) model was employed to forecast mortality trends from 2019 to 2023. Results: Over a recent 20-year period, the number of AD deaths in the U.S. increased from 44,536 (31,145 females and 13,391 males) to 122,019 (84,062 females and 37,957 males). The overall age-adjusted mortality rate increased from 16.5/100,000 in 1999 to 30.5/100,000 in 2018. AD mortality is projected to reach 42.40/100000 within the year 2023. Overall, AD resulted in 322,773.00 YLL (2.33 per 1000 population) in 1999 and 658,501.87 YLL (3.68 per 1000 population) in 2018. Conclusion: Our findings demonstrate an increase in AD mortality in the U.S. from 1999 to 2018 as well as a rapid increase from 2019 to 2023. The high burden of AD deaths emphasizes the need for targeted prevention, early diagnosis, and hierarchical management.

RNA polymerase III (Pol III) transcribes essential structured small RNAs, such as tRNAs, 5S rRNA and U6 snRNA. The transcriptional activity of Pol III is tightly controlled and its dysregulation is associated with human diseases, such as cancer. Human Pol III has two isoforms with difference only in one of its subunits RPC7 (α and β). Despite structural studies of yeast Pol III, structure of human Pol III remains unsolved. Here, we determined the structures of 17-subunit human Pol IIIα complex in the backtracked and post-translocation states, respectively. Human Pol III contains a generally conserved catalytic core, similar to that of yeast counterpart, and structurally unique RPC3-RPC6-RPC7 heterotrimer and RPC10. The N-ribbon of TFIIS-like RPC10 docks on the RPC4-RPC5 heterodimer and the C-ribbon inserts into the funnel of Pol III in the backtracked state but is more flexible in the post-translocation state. RPC7 threads through the heterotrimer and bridges the stalk and Pol III core module. The winged helix 1 domain of RPC6 and the N-terminal region of RPC7α stabilize each other and may prevent Maf1-mediated repression of Pol III activity. The C-terminal FeS cluster of RPC6 coordinates a network of interactions that mediate core-heterotrimer contacts and stabilize Pol III. Our structural analysis sheds new light on the molecular mechanism of human Pol IIIα-specific transcriptional regulation and provides explanations for upregulated Pol III activity in RPC7α-dominant cancer cells.

Immunoglobulin G (IgG) functionality can drastically change from anti- to proinflammatory by alterations in the IgG N-glycan patterns. Our previous studies have demonstrated that IgG N-glycans associated with the risk factors of dementia, such as aging, dyslipidemia, type 2 diabetes mellitus, hypertension, and ischemic stroke. Therefore, the aim is to investigate whether the effects of IgG N-glycan profiles on dementia exists in a Chinese Han population. A case–control study, including 81 patients with dementia, 81 age- and gender-matched controls with normal cognitive functioning (NC) and 108 non-matched controls with mild cognitive impairment (MCI) was performed. Plasma IgG N-glycans were separated by ultra-performance liquid chromatography. Fourteen glycan peaks reflecting decreased of sialylation and core fucosylation, and increased bisecting N-acetylglucosamine (GlcNAc) N-glycan structures were of statistically significant differences between dementia and NC groups after controlling for confounders (p q p q N-glycans might contribute to be potential novel biomarkers for the neurodegenerative process risk assessment of dementia.

Purpose Epilepsy is one of the most disabling neurological disorders, which affects all age groups and often results in severe consequences. Since misdiagnoses are common, many pediatric patients fail to receive the correct treatment. Recently, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging has been used for the evaluation of pediatric epilepsy. However, the epileptic focus is very difficult to be identified by visual assessment since it may present either hypo- or hyper-metabolic abnormality with unclear boundary. This study aimed to develop a novel symmetricity-driven deep learning framework of PET imaging for the identification of epileptic foci in pediatric patients with temporal lobe epilepsy (TLE). Methods We retrospectively included 201 pediatric patients with TLE and 24 age-matched controls who underwent 18F-FDG PET-CT studies. 18F-FDG PET images were quantitatively investigated using 386 symmetricity features, and a pair-of-cube (PoC)-based Siamese convolutional neural network (CNN) was proposed for precise localization of epileptic focus, and then metabolic abnormality level of the predicted focus was calculated automatically by asymmetric index (AI). Performances of the proposed framework were compared with visual assessment, statistical parametric mapping (SPM) software, and Jensen-Shannon divergence-based logistic regression (JS-LR) analysis. Results The proposed deep learning framework could detect the epileptic foci accurately with the dice coefficient of 0.51, which was significantly higher than that of SPM (0.24, P < 0.01) and significantly (or marginally) higher than that of visual assessment (0.31–0.44, P = 0.005–0.27). The area under the curve (AUC) of the PoC classification was higher than that of the JS-LR (0.93 vs. 0.72). The metabolic level detection accuracy of the proposed method was significantly higher than that of visual assessment blinded or unblinded to clinical information (90% vs. 56% or 68%, P < 0.01). Conclusion The proposed deep learning framework for 18F-FDG PET imaging could identify epileptic foci accurately and efficiently, which might be applied as a computer-assisted approach for the future diagnosis of epilepsy patients. Trial registration NCT04169581. Registered November 13, 2019 Public site: https://clinicaltrials.gov/ct2/show/NCT04169581

Backgrounds Night-shift workers are exposed to nocturnal light and are more prone to circadian rhythm disorders. Although night-shift work is thought to be associated with the decrease in melatonin secretion, studies have shown inconsistent results. Methods This systematic review and meta-analysis studied the association between night-shift work and melatonin levels. Pubmed and Embase databases were used for literature searching. The pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used to compare the differences between night-shift workers and the controls. Results Thirty-three studies reported in 25 articles (1845 night-shift workers and 3414 controls, mean age 45.12 years) were included after a systematic literature review. Data of circulating melatonin levels and its metabolites, 6-sulfatoxymelatonin (aMT6s) in urine were collected for meta-analysis. The results showed that the first morning-void aMT6s level in night-shift workers was significantly lower than in day workers (SMD = −0.101, 95% CI = −0.179 to −0.022, P = 0.012). The level of mean 24-h urinary aMT6s was lower in night-shift workers than day workers (SMD: −0.264, 95% CI: −0.473 to −0.056, P = 0.013). Among fixed night-shift workers, the level of circulating melatonin, as well as first morning-void aMT6s was lower than that of day workers. Conclusion Our findings indicate that experience of night-shift work is associated with suppression of melatonin production, especially among fixed night-shift workers.

Cardiovascular disease is a common complex trait that calls for next-generation biomarkers for precision diagnostics and therapeutics. The most common type of post-translational protein modificatio...

Type 2 diabetes mellitus (T2DM) is a common complex trait arising from interactions among multiple environmental, genomic, and postgenomic factors. We report here the first attempt to investigate the association between immunoglobulin G (IgG) N-glycan patterns, T2DM, and their clinical risk factors in an Australian population. N-glycosylation of proteins is one of the most frequently observed co- and post-translational modifications, reflecting, importantly, the real-time status of the interplay between the genomic and postgenomic factors. In a community-based case-control study, 849 participants (217 cases and 632 controls) were recruited from an urban community in Busselton, Western Australia. We applied the ultraperformance liquid chromatography method to analyze the composition of IgG N-glycans. We then conducted Spearman's correlation analyses to explore the association between glycan biomarker candidates and clinical risk factors. We performed area under the curve (AUC) analysis of the receiver operating characteristic curves by fivefold cross-validation for clinical risk factors, IgG glycans, and their combination. Two directly measured and four derived glycan peaks were significantly associated with T2DM, after correction for extensive clinical confounders and false discovery rate, thus suggesting that IgG N-glycan traits are highly correlated with T2DM clinical risk factors. Moreover, adding the IgG glycan profiles to fasting blood glucose in the logistic regression model increased the AUC from 0.799 to 0.859. The AUC for IgG glycans alone was 0.623 with a 95% confidence interval 0.580-0.666. In addition, our study provided new evidence of diversity in T2DM complex trait by IgG N-glycan stratification. Six IgG glycan traits were firmly associated with T2DM, which reflects an increased proinflammatory and biological aging status. In summary, our study reports novel associations between the IgG N-glycome and T2DM in an Australian population and the putative role of proinflammatory mechanisms. Furthermore, IgG N-glycomic alterations offer future prospects as inflammatory biomarker candidates for T2DM diagnosis, and monitoring of T2DM progression to cardiovascular disease or renal failure.

The increasing prevalence of hyperuricemia has been recognized as an emerging public health concern in both developed and developing countries. Hyperuricemia is a metabolic condition characterized by an elevated serum uric acid, and associated with renal damage, diabetes, autoimmune disorders, and cardiovascular diseases. Although human genetic variation has been recognized as a factor, posttranslational cellular processes and glycan biomarkers have not been studied extensively for susceptibility to hyperuricemia. We evaluated whether immunoglobulin (Ig)G N-glycans play a role in hyperuricemia in the general population. This cross-sectional study enrolled 635 participants (208 men and 427 women), ages ≥18 years, from a community-based population in Beijing, China. The IgG N-glycan composition of serum was analyzed by an ultraperformance liquid chromatography method. The prevalence of hyperuricemia observed in this sample was 5.98% (14.9% in men and 1.6% in women). Serum uric acid level was positively correlated with glycan peaks (GP)1, GP2, GP4, GP6, GP10, and GP11, whereas it was negatively correlated with GP12, GP13, GP14, GP15, GP18, and GP20. The combination of GP9, GP10, body mass index, and gender distinguished individuals with hyperuricemia from subjects without hyperuricemia, with an area under the curve value of 0.849 (95% confidence interval: 0.784-0.915). These findings collectively suggest a possible link between hyperuricemia and IgG N-glycans, which might be potentially mediated through inflammation-related mechanisms. Additional research on glycan biomarkers in independent and community-based population samples might allow the development of glycan diagnostics for hyperuricemia and gout in the future.

Background The mechanism by which normal body mass index (BMI) with central adiposity (NWCA) increases the risk of the diseases has not been completely elucidated. The inflammatory role of immunoglobulin G (IgG) N-glycosylation in obesity defined by BMI or central adiposity defined by waist-to-hip ratio (WHR) was reported, respectively. We undertook this three-center cross-sectional study to determine the association between the IgG N-glycans and NWCA. Methods The participants were categorized into four different phenotypes: normal BMI with normal WHR (NW), normal BMI with central adiposity (NWCA), obesity with normal WHR (ONCA) and obesity with central adiposity (OCA). The IgG N-glycans were analyzed using ultra-performance liquid chromatography analysis of released glycans, and differences among groups were compared. Results In total, 17 out of 24 initial IgG N-glycans were significantly different among the four groups (NW, ONCA, NWCA and OCA) (P

Background. Extensive studies have been carried out to investigate the association between obesity and the risk of rheumatoid arthritis (RA); however, the results of the current reported original studies remain inconsistent. This study aimed to clarify the relationship between body mass index and rheumatoid arthritis by conducting an updated overall and dose-response meta-analysis. Methods. The relevant literature was searched using the PubMed and Embase databases (through 20 September 2018) to identify all eligible published studies. Random-effect models and dose-response meta-analyses were used to estimate the pooled risk ratio (RR) with a 95% confidence interval (CI). Subgroup analyses were also conducted based on the characteristics of the participants. Sensitivity analyses and publication bias tests were also performed to explore potential heterogeneity and bias in the meta-analysis. Results. Sixteen studies that included a total of 406,584 participants were included in the meta-analysis. Compared to participants with normal weight, the pooled RRs of rheumatoid arthritis were 1.12 (95% CI, 1.04-1.20) in overweight and 1.23 (95% CI, 1.09-1.39) in obese participants. There was evidence of a nonlinear relationship between body mass index (BMI) and RA (P for nonlinearity less than 0.001 in the overall meta-analysis, P for nonlinearity=0.025 in the case-control studies, P for nonlinearity=0.0029 in the cohort studies). No significant heterogeneity was found among studies (I2=10.9% for overweight and I2=45.5% for obesity). Conclusion. The overall and dose-response meta-analysis showed that increased BMI was associated with an increased risk for rheumatoid arthritis, which might present a prevention strategy for the prevention or control of rheumatoid arthritis. The nonlinear relationship between BMI and RA might present a personal prevention strategy for RA.

IntroductionProfiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%–40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk.Methods and analysisThe prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness–implementation hybrid design, taking place in the UK and China. People are eligible if they are 55–75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention.Ethics and disseminationThe PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London—Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People’s Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal.Trial registration numberISRCTN15986016.

Mammary gland hyperplasia (MGH) is very common, especially among young and middle-aged women. New diagnostics and biomarkers for MGH are needed for rational clinical management and precision medicine. We report, in this study, new findings using a glycomics approach, with a focus on immunoglobulin G (IgG) N-glycosylation. A cross-sectional study was conducted in a community-based population sample in Beijing, China. A total of 387 participants 40–65 years of age were enrolled in this study, including 194 women with MGH (cases) and 193 women who had no MGH (controls). IgG N-glycans were characterized in the serum by ultra-performance liquid chromatography. The levels of the glycan peaks (GPs) GP2, GP5, GP6, and GP7 were lower in the MGH group compared with the control group, whereas GP14 was significantly higher in the MGH group (p

BACKGROUND Metabolically healthy obesity (MHO) and metabolically healthy overweight (MH-OW) have been suggested to be important and emerging phenotypes with an increased risk of cardiovascular disease (CVD). However, whether MHO and MH-OW are associated with all-cause mortality remains inconsistent. METHODS The association of MHO and MH-OW and all-cause mortality was determined in a Chinese community-based prospective cohort study (the Kailuan study), including 93,272 adults at baseline. Data were analyzed from 2006 to 2017. Participants were categorized into 6 mutually exclusive groups, according to BMI and metabolic syndrome (MetS) status. The primary outcome was all-cause death, and accidental deaths were excluded. RESULTS During a median follow-up of 11.04 years (interquartile range, 10.74–11.22 years), 8977 deaths occurred. Compared with healthy participants with normal BMI (MH-NW), MH-OW participants had the lowest risk of all-cause mortality (multivariate-adjusted HR [aHR], 0.926; 95% CI, 0.861–0.997), whereas there was no increased or decreased risk for MHO (aHR, 1.009; 95% CI, 0.886–1.148). Stratified analyses and sensitivity analyses further validated that there was a nonsignificant association between MHO and all-cause mortality. CONCLUSIONS Overweight and obesity do not predict increased risk of all-cause mortality in metabolic healthy Chinese individuals. FUNDING National Natural Science Foundation of China (NSFC; 81673247, 81872682 and 81773527), the NSFC Joint Project, and the Australian National Health and Medical Research Council (NHMRC; NSFC 81561128020-NHMRC APP1112767)., Obesity does not predict increased risk of all-cause mortality in metabolic healthy Chinese individuals.

Assembling for transcription initiation Eukaryotic transcription initiation by RNA polymerase II (Pol II) requires the assembly of a preinitiation complex (PIC) on core promoters. The binding of TATA box–binding protein (TBP) to the TATA box promoter has been thought to be a general rule in PIC assembly and transcription initiation. However, most coding genes lack a TATA box, and nearly all Pol II–mediated gene transcription requires the TBP-containing multisubunit complex transcription factor IID (TFIID). Chen et al. determined the structures of human TFIID-based PIC in sequential assembly states and revealed that TFIID supports distinct PIC assembly on TATA-containing and TATA-lacking promoters. The finding resolves the long-standing mystery of how one set of general transcription machinery initiates transcription on diverse promoters. Science , this issue p. eaba8490

Background: Nightshift work introduces light at night and causes circadian rhythm among night workers, who are considered to be at increased risk of cancer. However, in the last 2 years, nine population-based studies reported insignificant associations between night-shift work and cancer risks. We aimed to conduct an updated systematic review and meta-analysis to ascertain the effect of night-shift work on the incidence of cancers. Methods: Our protocol was registered in PROSPERO and complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Embase, PubMed, and Web of Science databases were used to comprehensively search studies published up to May 31, 2019. The random-effect model (Der Simonian-Laird method) was carried out to combine the risk estimates of night-shift work for cancers. The dose-response meta-analysis was performed to verify whether the association was in a dose-dependent manner. Results: Our literature searching retrieved 1,660 publications. Included in the meta-analyses were 57 eligible studies with 8,477,849 participants (mean age 55 years; 2,560,886 men, 4,220,154 women, and 1,696,809 not mentioned). The pooled results showed that night-shift work was not associated with the risk of breast cancer (OR = 1.009, 95% CI = 0.984-1.033), prostate cancer (OR = 1.027, 95% CI = 0.982-1.071), ovarian cancer (OR = 1.027, 95% CI = 0.942-1.113), pancreatic cancer (OR = 1.007, 95% CI = 0.910-1.104), colorectal cancer (OR = 1.016, 95% CI = 0.964-1.068), non-Hodgkin's lymph (OR = 1.046, 95% CI = 0.994-1.098), and stomach cancer (OR = 1.064, 95% CI = 0.971-1.157), while night-shift work was associated with a reduction of lung cancer (OR = 0.949, 95% CI = 0.903-0.996), and skin cancer (OR = 0.916, 95% CI = 0.879-0.953). The dose-response meta-analysis found that cancer risk was not significantly elevated with the increased light exposure of night- shift work. Conclusion: This systematic review of 57 observational studies did not find an overall association between ever-exposure to night-shift work and the risk of breast, prostate ovarian, pancreatic, colorectal, non-Hodgkin's lymph, and stomach cancers.

Prospective studies have shown that abnormally circulating cholesterol is associated with the risk of dementia. However, whether the association is causal or not remains unclear. We attempt to infer the causal association in a MR meta-analysis by using ApoE gene polymorphisms as instrument variables. Studies with dementia risk (27 studies) or circulating lipid levels (7 studies) were included, with totally 3136 dementia patients and 3103 healthy controls. The analyses showed that carriers of ε2 allele significantly were of decreased risk of AD (OR = 0.70; 95% CI: 0.58–0.84; P P P P P P P P

Background Suboptimal health status (SHS) is an intermediate health status between ideal health and illness. As a determinant of cardiovascular disease and stroke, SHS is hypothesized to be associated with the development of cognitive impairment and dementia. This study aimed to investigate whether individuals with SHS have poor cognitive ability based on a community-based cohort in northern Chinese population. Methods 3524 participants who were enrolled in Jidong cohort 2015 in Tangshan City were investigated in this study. Cognitive function was measured with the Mini-Mental State Examination (MMSE). SHS level was evaluated using a self-reporting Suboptimal Health Status Questionnaire-25 (SHSQ-25). The relationship between SHS and cognitive function was analyzed with logistic regression analysis, by which odds ratio (OR) and 95% confidence interval (CI) were calculated. Results The prevalence of cognitive impairment was 3.4% (121/3524) in our study, with the prevalence rates of 1.9% (34/1750) among men and 4.9% (87/1774) in women. The medians of total score of MMSE were 28 (interquartile range (IQR) = 27-29) in the SHS group, and 29 (IQR = 27-30) in the ideal health group. Logistic regression analysis showed that SHS was significantly correlated with cognitive impairment (adjusted OR = 2.936, 95% CI = 1.428-6.033). With regard to gender, the OR was 5.067 (95% CI = 1.346-19.068) in men, which was higher than that in women (OR = 2.324, 95% CI = 1.130-4.779). Conclusions SHS might be a risk factor for cognitive function in northern Chinese population. Early screening of SHS individuals, as well as urgent treatment of SHS might contribute to the prevention of cognitive impairment.

Epilepsy that originates outside of the temporal lobe can present some of the most challenging problems for surgical therapy, especially for patients with conventional magnetic resonance imaging (MRI)-negative refractory extra-temporal lobe epilepsy (ETLE). This study aimed to evaluate the clinical value of pre-surgical 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) and high-resolution MRI (HR-MRI) co-registration in patients with conventional MRI-negative refractory ETLE, and compare their surgical outcomes. Sixty-seven patients with conventional MRI-negative refractory ETLE were prospectively included for pre-surgical 18F-FDG PET and HR-MRI examinations. Under the guidance of 18F-FDG PET and HR-MRI co-registration, HR-MRI images were re-read. Based on the image result changes from first reading to re-reading, patients were divided into three groups: Change-1 (lesions of subtle abnormality could be identified in re-read), Change-2 (non-specific abnormalities reported in the first reading were considered as lesions on HR-MRI re-read) and No-change. Post-surgical follow-ups were conducted for up to 59 months. Visual analysis of 18F-FDG PET showed focal or regional abnormality in 46 patients (68.6%), while the abnormal rate increased to 94.0% (P

Non-medical use of prescription opioids, especially among adolescents, has been substantially increased in recent years. However, the neuromechanism remains largely unexplored. In the present study, we aimed to investigate the brain metabolic changes in adolescent rats following chronic escalating morphine administration using positron emission tomography (PET). 2-Deoxy-2-[18F]Fluoro-d-glucose ([18F]FDG) microPET imaging was performed, and statistical parametric mapping (SPM) was used for image analysis. Glucose transporter 3 (Glut-3), dopamine D2 receptor (D2R), and Mμ-opioid receptor (μ-OR) were used for immunostaining analysis. Cerebral glucose metabolism was increased in the corpus callosum (CC) and right retrosplenial dysgranular cortex (rRSD), while it was decreased in the right ventral pallidum (rVP). The expressions of Glut-3, D2R, and μ-OR were increased in CC and rRSD, while they were decreased in rVP. Furthermore, glucose metabolism and Glut-3 expression were positively correlated with the expressions of D2R or μ-OR in CC, rRSD, and rVP. [18F]FDG microPET brain imaging study in combination with immunohistological investigation revealed that CC, rRSD, and rVP were specifically involved in opioid dependence in adolescents. Our findings provided valuable insights into the neuromechanism of adolescent addiction of prescription opioids and might have important implications for the development of prevention and intervention approaches.

BACKGROUND This study aimed to retrospectively analyze patient clinical data to investigate the effects of computed tomography (CT) reconstruction and the measurement of abnormal structures in the endonasal sphenoidal sinus approach on the operative effects in patients undergoing pituitary adenoma resection. MATERIAL AND METHODS The records of 53 patients who underwent pituitary adenoma resection via the endonasal transsphenoidal approach in the Neurosurgery Department of Tai'an City Central Hospital from December 2010 to June 2016 were analyzed retrospectively. All cases showed anatomical abnormalities in the endonasal transsphenoidal approach that were detected by conventional CT scans. The clinical data of the patients were reviewed. After review, 26 patients who underwent preoperative CT reconstruction and measurement of abnormal structures before surgery were included in the observation group (CT reconstruction group), and 27 patients who did not undergo CT reconstruction and measurement of abnormal structures were included in the control group. Data on intraoperative blood loss, surgical time, hospital stay, and postoperative complications were collected to assess the quality of the surgery. RESULTS Compared with the control group, the observation group showed less blood loss (p

[11C]-S-methyl-16-thiopalmitic acid (a) was developed with excellent heart-to-background uptake ratios and higher retention in heart. Myocardial uptake and metabolism of the tracer is markedly higher CPT I dependent. When compared to [11C]-S-methyl-14-thiomyristic acid (b), [11C]-S-methyl-12-thiododecanoic acid (c) and [11C]-palmitate, a showed an early high uptake and a significantly slower late clearance in heart and a prolonged myocardial elimination half-life (30 min). Analysis of heart tissue and urine samples showed that a was metabolized via beta-oxidation in myocardium. Small animal PET images of the accumulation of a in the rat myocardium were clearly superior to [11C]-palmitate. These initial studies suggest that a could be a potentially useful clinical PET tracer to assess myocardial fatty acid metabolism.

Coronary artery disease (CAD) is a significant contributor to global health burden. Adiponectin gene single nucleotide polymorphisms (SNPs) have been associated with CAD susceptibility, but with inconsistent results across the studies. We present, in this study, an updated meta-analysis to discern the genetic susceptibility of adiponectin SNPs in relation to CAD. PubMed and EMBASE databases were used to identify the relevant published articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios and 95% confidence intervals were generated to assess the strength of the associations. Thirty-five articles with a total of 28,947 participants (mean age 55.3 years, 11,632 cases/17,315 controls, 19,443 males/8353 females, and 1151 persons with unspecified gender data) were included. The dominant, recessive, and additive models were applied. We found that the SNPs +45TG (rs2241766), -4034AC (rs822395), and -11391GA (rs17300539) were linked to CAD development. In addition, +276GT (rs1501299) SNP was associated with a decreased susceptibility to CAD among Caucasians. We did not find an association between the CAD susceptibility and the -11377CG (rs266729) SNP. These observations offer new potential genetic biomarker candidates in relation to CAD, and warrant further research in independent world populations.

Background: Esophageal cancer (EC) causes more than 400 thousand deaths per year, and half of them occur in China. There are discrepancies regarding the survival of EC patients between population-based surveillance studies and hospital-based studies. Objectives: We aimed to synthesize the survival data from hospital-based EC studies in the Chinese population from 2000 to 2018 and to compare the survival rates between EC patients with different clinical classifications. Methods: The protocol of this systematic review was registered in PROSPERO (CRD-42019121559). We searched Embase, PubMed, CNKI, and Wanfang databases for studies published between January 1, 2000 and December 31, 2018. We calculated the pooled survival rates and 95% confidence intervals (CIs) by Stata software (V14.0). Results: Our literature search identified 933 studies, of which 331 studies with 79,777 EC patients met the inclusion criteria and were included in meta-analyses. The pooled survival rates were 74.1% (95% CI: 72.6-75.7%) for 1-year survival, 49.0% (95% CI: 44.2-53.8%) for 2-years survival, 46.0% (95% CI: 42.6-49.5%) for 3-years survival, and 40.1% (95% CI: 33.7-46.4%) for 5-years survival. An increased tendency toward EC survival was verified from 2000 to 2018. In addition, discrepancies were observed between EC patients with different clinical classifications (e.g., stages, histologic types, and cancer sites). Conclusions: Our findings showed a higher survival rate in hospital-based studies than population-based surveillance studies. Although this hospital-based study is subject to potential representability and publication bias, it offers insight into the prognosis of patients with EC in China.

PET with 18F-FDG has been used for presurgical localization of epileptogenic foci; however, in nonsurgical patients, the correlation between cerebral glucose metabolism and clinical severity has not been fully understood. The aim of this study was to evaluate the glucose metabolic profile using 18F-FDG PET/CT imaging in patients with epilepsy. Methods: One hundred pediatric epilepsy patients who underwent 18F-FDG PET/CT, MRI, and electroencephalography examinations were included. Fifteen age-matched controls were also included. 18F-FDG PET images were analyzed by visual assessment combined with statistical parametric mapping (SPM) analysis. The absolute asymmetry index (|AI|) was calculated in patients with regional abnormal glucose metabolism. Results: Visual assessment combined with SPM analysis of 18F-FDG PET images detected more patients with abnormal glucose metabolism than visual assessment only. The |AI| significantly positively correlated with seizure frequency (P < 0.01) but negatively correlated with the time since last seizure (P < 0.01) in patients with abnormal glucose metabolism. The only significant contributing variable to the |AI| was the time since last seizure, in patients both with hypometabolism (P = 0.001) and with hypermetabolism (P = 0.005). For patients with either hypometabolism (P < 0.01) or hypermetabolism (P = 0.209), higher |AI| values were found in those with drug resistance than with seizure remission. In the post-1-y follow-up PET studies, a significant change of |AI| (%) was found in patients with clinical improvement compared with those with persistence or progression (P < 0.01). Conclusion:18F-FDG PET imaging with visual assessment combined with SPM analysis could provide cerebral glucose metabolic profiles in nonsurgical epilepsy patients. |AI| might be used for evaluation of clinical severity and progress in these patients. Patients with a prolonged period of seizure freedom may have more subtle (or no) metabolic abnormalities on PET. The clinical value of PET might be enhanced by timing the scan closer to clinical seizures.

BACKGROUND This investigation aimed to evaluate changes in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of white matter injury (WMI) in preterm neonates with hypoxic-ischemic encephalopathy (HIE) using diffusion tension imaging (DTI). MATERIAL AND METHODS Thirty-eight neonates less than 37 weeks of gestation with leukoencephalopathy (as observation group) and 38 full-term infants with no leukoencephalopathy (as control group) were selected from the Neonatal Care Center in Taian Central Hospital from January 2012 to December 2013. A DTI scan was obtained within 1 week after birth. RESULTS In the observation group, on both sides the ADC values in regions of interest (ROI) of white matter, lesions were greater and FA values were lower than in the control group. ADC and FA values in genu and splenum of corpus callosum were statistically different between the mild and severe injury groups (p

BACKGROUND: Selective reporting of results in published case-control studies has been widely suspected, but little comprehensive information on selective reporting is available with regard to case-control studies. We aimed to evaluate the concordance of findings between publications and the protocols of case-control studies and to assess the level of selective reporting of results in case-control studies. METHODS: The databases of Embase, Medline, Scopus, and Web of Science were searched to identify case-control study protocols published between January 1, 1990 and December 31, 2017. The numbers and characteristics of predefined exposures (or factors) were extracted from the protocols. The reported and unreported factors were both collected from the published studies and protocols. The frequency of selective reporting of results were estimated by identifying the discrepancies of factors between the protocols and the published studies. Study sample size and the extent of selective reporting of factors were measured by a Spearman correlation analysis. RESULTS: Fourteen protocols with 24 published studies and 159 factors were identified, of which eight protocols (57.1%) had discrepancies between the publications and protocols. The prevalence of incomplete reporting in published case-control studies was 42.9% (6/14), with participant characteristics, anthropometric and laboratory measurement variables more likely to be unreported. A total of 16,835 cases and 56,049 controls were recruited in the 14 protocols of case-control studies (sample size ranges from 428 to 52,596 per study). Sample size had no statistical significance with selective reporting of results (P > 0.05). CONCLUSION: The study protocols should be publicly available prior to the completion of case-control studies so that the potential bias can be assessed by the readers. Our findings highlight the need for investigators, peer reviewers, and readers to exercise increased awareness and scrutiny due to the undesirable practice of selective reporting of results in medical sciences causing the loss of potentially important information, thus impacting quality of personalized attitude in healthcare in the context of the predictive, preventive, and personalized medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13167-019-00165-2) contains supplementary material, which is available to authorized users.

BACKGROUND: The prevalence of diabetes, constituted chiefly by type 2 diabetes mellitus (T2DM), is a global public health threat. Suboptimal health status (SHS), a physical state between health and disease, might contribute to the progression or development of T2DM. METHODS: We conducted a prospective cohort study, based on the China Suboptimal Health Cohort Study (COACS), to understand the impact of SHS on the progress of T2DM. We examined associations between SHS and T2DM outcomes using multivariable logistic regression models and constructed predictive models for T2DM onset based on SHS. RESULTS: A total of 61 participants developed T2DM after an average of 3.1 years of follow-up. Participants with higher SHS scores had more T2DM outcomes (p = 0.036). Moreover, compared with the lowest quartile of SHS scores, participants with fourth, third, and second quartile SHS scores were found to be associated with a 1.7-fold, 1.6-fold, and 1.5-fold risk of developing T2DM, respectively. The predictive model constructed with SHS had higher discriminatory power (AUC = 0.848) than the model without SHS (AUC = 0.795). CONCLUSIONS: The present study suggests that a higher SHS score is associated with a higher incidence of T2DM. SHS is a new independent risk factor for T2DM and has the capability to act as a predictive tool for T2DM onset. The evaluation of SHS combined with the analysis of modifiable risk factors for SHS allows the risk stratification of T2DM, which may consequently contribute to the prevention of T2DM development. These findings might require further validation in a longer-term follow-up study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13167-019-0159-9) contains supplementary material, which is available to authorized users.

BACKGROUND: Suboptimal health status (SHS) is an intermediate health status between health and illness, a syndrome characterised by the perception of health complaints, general weakness and low energy. This study aimed to investigate the prevalence of SHS and the correlation between SHS and psychological symptoms among Chinese college students and to identify the SHS-related risk factors from the perspective of predictive, preventive and personalised medicine (PPPM). METHODS: A cross-sectional study was conducted among 4119 college students who were enrolled from Taishan Medical University and Baoji Vocational and Technical College in the eastern and western areas of China. SHS levels of the participants were measured by an established self-reporting Suboptimal Health Status Questionnaire-25 (SHSQ-25). Psychosomatic conditions were estimated by the self-rating Symptom Checklist-90 (SCL-90) scale. Spearman correlation analysis was applied to analyse the relationship between SHSQ-25 scores and SCL-90 estimates. Logistic regression analysis was applied for multivariate analysis. RESULTS: The prevalence of SHS was 21.0% (864/4119), with 23.3% (701/3005) for female students and 14.6% (163/1114) for male students. The prevalence of general positive psychological symptom was 14.2% (586/4119), with 15.6% (470/3005) for female students and 10.4% (116/1114) for male students. A strong correlation was identified between SHS score and SCL-90 estimates, with the correlation coefficient (r) of 0.719. Logistic regression showed that variables significantly associated with SHS were somatisation (adjusted odds ratio (aOR) = 3.185, 95% confidence interval [CI] = 2.048–4.953), obsessive-compulsive (aOR = 3.518, 95% CI = 2.834–4.368), interpersonal sensitivity (aOR = 1.883, 95% CI = 1.439–2.463) and depression (aOR = 1.847, 95% CI = 1.335–2.554). CONCLUSIONS: Our findings confirm that there is a high prevalence of SHS among college students and there is a strong association between SHS and psychological symptoms among Chinese college students. High susceptibility of SHS occurs particularly in vulnerable groups: female students, sophomore students, medical students and students from rural area. Identification of SHS and prompt application of personalised psychological health-supporting activities will promote college students’ health status. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13167-018-0148-4) contains supplementary material, which is available to authorized users.

Background Obstructive sleep apnea (OSA) is a sleep disorder characterized as complete or partial upper airflow cessation during sleep. Although it has been widely accepted that OSA is a risk factor for the development of hypertension, the studies focusing on this topic revealed inconsistent results. We aimed to clarify the association between OSA and hypertension, including essential and medication-resistant hypertension. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. PubMed and Embase databases were used for searching the relevant studies published up to December 31, 2016. A quantitative approach of meta-analysis was performed to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). Results Twenty-six studies with 51 623 participants (28 314 men, 23 309 women; mean age 51.8 years) met inclusion criteria and were included in this study. Among them, six studies showed a significant association between OSA and resistant hypertension (pooled OR = 2.842, 95% CI = 1.703-3.980, P

BACKGROUND Red cell distribution width (RDW) is a cardiac marker for risk stratification and prognostic evaluation of coronary artery disease (CAD); however, the underlying mechanism remains unclear. Erythropoietin (EPO), a crucial factor affecting erythropoiesis, has been reported to be a protective molecule regulating the process of myocardial ischemia and relevant damage. No study has as yet reported the relationship between RDW and endogenous EPO in CAD patients. This cross-sectional study aimed to establish the association between endogenous EPO levels and increases in RDW in CAD patients. PATIENTS AND METHODS Two hundred participants who underwent coronary arteriography were recruited from July 2015 to October 2015. The participants were divided into CAD and non-CAD groups on the basis of angiography diagnosis. Demographic data were obtained through personal interviews and general clinical methods. RESULTS RDW and EPO levels in the CAD group were higher than those in the non-CAD group. The correlation between RDW and EPO levels was statistically significant among CAD patients (r=0.411, P

Red blood cell distribution width (RDW) is the coefficient of variation of red blood cell size, considered to be associated with cardiovascular disease (CVD). This study aimed to comprehensively synthesize previous studies on RDW and CVD outcomes through an overall and dose-response meta-analysis. PubMed, Embase and Web of Science were searched systematically for English and Chinese language publications up to November 30, 2015. We extracted data from publications matching our inclusion criteria for calculating pooled hazard ratio (HR), which was used to assess prognostic impact of RDW on CVD. Twenty-seven articles, consisting of 28 studies and 102,689 participants (mean age 63.9 years, 63,703 males/36,846 females, 2,140 gender-unmentioned subjects) were included in the present meta-analysis. The pooled HRs are 1.12 (95% CI = 1.09–1.15) for the association of all-cause mortality (ACM) per 1% increase of RDW, 1.12(95% CI = 1.08–1.17) for major adverse cardiac events (MACEs) per 1% increase of RDW. A dose-response curve relating RDW increase to its effect on CVD outcomes was established (pcurve

Background Flood-related damage can be very severe and include health effects. Among those health impacts, infectious diseases still represent a significant public health problem in China. However, there have been few studies on the identification of the spectrum of infectious diseases associated with floods in one area. This study aimed to quantitatively identify sensitive infectious diseases associated with floods in Guangxi, China. Methods A time-trend ecological design was conducted. A descriptive analysis was first performed to exclude infectious diseases with low incidence from 2005 to 2012 in ten study sites of Guangxi. The Wilcoxon rank-sum test was applied to examine the difference in the ten-day attack rate of infectious diseases between the exposure and control periods with different lagged effects. Negative binomial, zero-inflated Poisson and zero-inflated negative binomial models were used to examine the relationship and odd ratios (ORs) of the risk of floods on infectious diseases of preliminary screening. Results A total of 417,271 infectious diseases were notified. There were 11 infectious diseases associated with floods in the preliminary screening process for flood-sensitive infectious diseases. The strongest effect was shown with a 0–9 ten-day lag in different infectious diseases. Multivariate analysis showed that floods were significantly associated with an increased the risk of bacillary dysentery (odds ratio (OR) = 1.268, 95% confidence interval (CI): 1.072–1.500), acute haemorrhagic conjunctivitis (AHC, OR = 3.230, 95% CI: 1.976–5.280), influenza A (H1N1) (OR = 1.808, 95% CI: 1.721–1.901), tuberculosis (OR = 1.200, 95% CI: 1.036–1.391), influenza (OR = 2.614, 95% CI: 1.476–4.629), Japanese encephalitis (OR = 2.334, 95% CI: 1.119–4.865), and leptospirosis (OR = 1.138, 95% CI: 1.075–1.205), respectively. Conclusion The spectrum of infectious diseases which are associated with floods are bacillary dysentery, AHC, influenza A (H1N1), tuberculosis, influenza, Japanese encephalitis and leptospirosis in Guangxi. Floods can result in differently increased risk of these diseases, and public health action should be taken to control a potential risk of these diseases after floods., Highlights • The health effects of floods on infectious diseases are complex and far-reaching. • First time to quantitatively identify sensitive infectious diseases associated with floods. • Floods have different impacts on sensitive infectious diseases and bring more risk of AHC and influenza.

Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from the MEGASTROKE collaboration with 40,585 stroke cases and 406,111 controls. The weighted median (WM), the penalized weighted median (PWM), the inverse variance weighted (IVW), the penalized inverse variance weighted (PIVW), the robust inverse variance weighted (RIVW), and the Mendelian randomization-Egger (MR-Egger) methods were conducted for the MR analysis to estimate a causal effect and detect the directional pleiotropy. Results: No significant association between genetically determined TL with overall IS, LAS, or CES were found (all p &gt, 0.05). SVS was associated with TL by the RIVW method (odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.54&ndash, 0.97, p = 0.028), after excluding rs9420907, rs10936599, and rs2736100. Conclusions: By a series of causal inference approaches using SNPs as IVs, no strong evidence to support the causal effect of shorter TL on IS and its subtypes were found.

A landmark study from the Institute of Medicine reported that the assessment of cognitive difficulties in children with epilepsy is timely and imperative. Anticonvulsant-induced cognitive impairment could influence the quality of life more than seizure itself in patients. Although the monoaminergic system is involved in the regulation of cognitive process, its role in anticonvulsant-induced cognitive impairment remains unclear. Methods: To explore in vivo monoamine receptor binding activity in patients with anticonvulsant-induced cognitive impairment, each patient underwent PET imaging with both monoamine receptor binding agent 11C-N-methylspiperone and glucose metabolic agent 18F-FDG. Tests of intelligence quotient (IQ), including verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ), were performed in each patient. Results: Compared with the patients with monotherapy, patients with polytherapy had significantly lower VIQ, PIQ, and FSIQ (P 0.05). Conclusion: Monoamine receptor PET imaging could be a promising in vivo imaging biomarker for mapping anticonvulsant-induced cognitive impairment.

Music can induce different emotions. However, its neural mechanism remains unknown. The aim of this study was to use functional magnetic resonance imaging (fMRI) and position emission tomography (PET) imaging for mapping of neural changes under the most popular music in healthy volunteers. Blood-oxygen-level-dependent (BOLD) fMRI and monoamine receptor PET imaging with 11C-N-methylspiperone (11C-NMSP) were conducted under the popular music Gangnam Style and light music A Comme Amour in healthy subjects. PET and fMRI images were analyzed by using the Statistical Parametric Mapping software (SPM). Significantly increased fMRI BOLD signals were found in the bilateral superior temporal cortices, left cerebellum, left putamen and right thalamus cortex. Monoamine receptor availability was increased significantly in the left superior temporal gyrus and left putamen, but decreased in the bilateral superior occipital cortices under the Gangnam Style compared with the light music condition. Significant positive correlation was found between 11C-NMSP binding and fMRI BOLD signals in the left temporal cortex. Furthermore, increased 11C-NMSP binding in the left putamen was positively correlated with the mood arousal level score under the Gangnam Style condition. Popular music Gangnam Style can arouse pleasure experience and strong emotional response. The left putamen is positively correlated with the mood arousal level score under the Gangnam Style condition. Our results revealed characteristic patterns of brain activity associated with Gangnam Style, and may also provide more general insights into the music-induced emotional processing.

Introduction: The prevalence of deep vein thrombosis (DVT) and its risk factors in patients with cervical spondylotic myelopathy (CSM) before spinal surgery are poorly understood. We investigated this association with a retrospective cross-sectional study. Patients concerns: The study cohort consisted of all consecutive patients with CSM who were scheduled for spinal surgery at our institution from 2013 to 2015. DVT was defined as an intraluminal filling defect in a lower extremity vein identified by Doppler ultrasonography. Outcomes: Of the 396 patients with CSM, 16 (4%) had DVT. Compared with patients without preoperative DVT, patients with preoperative DVT were older (62.75 ± 8.79 vs 53.03 ± 10.95 years, P = 0.001), had higher D-dimer concentrations (2.23 ± 4.15 vs 0.43 ± 0.90 mg/L, P = 0.04), had experienced longer duration of CSM (7.56 ± 7.08 vs 4.01 ± 6.37 months, P = 0.03), had lower Japanese Orthopaedic Association lower limb motor dysfunction scores (1.68 ± 1.25 vs 2.54 ± 0.91, P = 0.01), and had a history of ischemic cardiovascular events (33.3% vs 2.1%, P = 0.02). The area under the curve for the ability of D-dimer levels to predict DVT was 0.858 (95% confidence interval: 0.764–0.951; P

Objective:Obesity is considered as one of the risk factors of kidney cancer. However, the results are not consistent in reported original studies, as well as in published meta-analysis. This study aims to clarify the relationship between overweight/obesity and kidney cancer by an updated ove