Kinase CPK10 regulates low light-induced tomato flower drop downstream of IDL6 in a calcium-dependent manner.

Flower drop is a major cause for yield loss in many crops. Previously, we found that tomato (Solanum lycopersicum) INFLORESCENCE DEFICIENT IN ABSCISSION-Like (SlIDL6) contributes to flower drop induced by low light. However, the molecular mechanisms by which SlIDL6 acts as a signal to regulate low light-induced abscission remain unclear. In this study, SlIDL6 was found to elevate cytosolic Ca2+ concentrations ([Ca2+]cyt) in the abscission zone (AZ), which was required for SlIDL6-induced flower drop under low light. We further identified that one calcium-dependent protein kinase gene (SlCPK10) was highly expressed in the AZ and up-regulated by SlIDL6-triggered [Ca2+]cyt. Over-expression and knockout of SlCPK10 in tomato resulted in accelerated and delayed abscission, respectively. Genetic evidence further indicated that knockout of SlCPK10 significantly impaired the function of SlIDL6 in accelerating abscission. Furthermore, Ser-371 phosphorylation in SlCPK10 dependent on SlIDL6 was necessary and sufficient for its function in regulating flower drop, probably by stabilizing the SlCPK10 proteins. Taken together, our findings reveal that SlCPK10, as a downstream component of the IDL6 signaling pathway, regulates flower drop in tomato under low light stress.

A SlCLV3-SlWUS module regulates auxin and ethylene homeostasis in low light-induced tomato flower abscission.

Premature abscission of flowers and fruits triggered by low light stress can severely reduce crop yields. However, the underlying molecular mechanism of this organ abscission is not fully understood. Here, we show that a gene (SlCLV3) encoding CLAVATA3 (CLV3), a peptide hormone that regulates stem cell fate in meristems, is highly expressed in the pedicel abscission zone (AZ) in response to low light in tomato (Solanum lycopersicum). SlCLV3 knockdown and knockout lines exhibit delayed low light-induced flower drop. The receptor kinases SlCLV1 and BARELY ANY MERISTEM1 function in the SlCLV3 peptide-induced low light response in the AZ to decrease expression of the transcription factor gene WUSCHEL (SlWUS). DNA affinity purification sequencing identified the transcription factor genes KNOX-LIKE HOMEDOMAIN PROTEIN1 (SlKD1) and FRUITFULL2 (SlFUL2) as SlWUS target genes. Our data reveal that low light reduces SlWUS expression, resulting in higher SlKD1 and SlFUL2 expression in the AZ, thereby perturbing the auxin response gradient and causing increased ethylene production, eventually leading to the initiation of abscission. These results demonstrate that the SlCLV3-SlWUS signaling pathway plays a central role in low light-induced abscission by affecting auxin and ethylene homeostasis.

SlBEL11 regulates flavonoid biosynthesis, thus fine-tuning auxin efflux to prevent premature fruit drop in tomato.

Auxin regulates flower and fruit abscission, but how developmental signals mediate auxin transport in abscission remains unclear. Here, we reveal the role of the transcription factor BEL1-LIKE HOMEODOMAIN11 (SlBEL11) in regulating auxin transport during abscission in tomato (Solanum lycopersicum). SlBEL11 is highly expressed in the fruit abscission zone, and its expression increases during fruit development. Knockdown of SlBEL11 expression by RNA interference (RNAi) caused premature fruit drop at the breaker (Br) and 3 d post-breaker (Br+3) stages of fruit development. Transcriptome and metabolome analysis of SlBEL11-RNAi lines revealed impaired flavonoid biosynthesis and decreased levels of most flavonoids, especially quercetin, which functions as an auxin transport inhibitor. This suggested that SlBEL11 prevents premature fruit abscission by modulating auxin efflux from fruits, which is crucial for the formation of an auxin response gradient. Indeed, quercetin treatment suppressed premature fruit drop in SlBEL11-RNAi plants. DNA affinity purification sequencing (DAP-seq) analysis indicated that SlBEL11 induced expression of the transcription factor gene SlMYB111 by directly binding to its promoter. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay showed that S. lycopersicum MYELOBLASTOSIS VIRAL ONCOGENE HOMOLOG111 (SlMYB111) induces the expression of the core flavonoid biosynthesis genes SlCHS1, SlCHI, SlF3H, and SlFLS by directly binding to their promoters. Our findings suggest that the SlBEL11-SlMYB111 module modulates flavonoid biosynthesis to fine-tune auxin efflux from fruits and thus maintain an auxin response gradient in the pedicel, thereby preventing premature fruit drop.

Enhanced photocatalytic ammonia oxidation activity and nitrogen selectivity over Ag/AgCl/N-TiO2 photocatalyst.

The removal of ammonia (NH3) emitted from agricultural and industrial activities is of great significance to protect human health and ecological environment. Photocatalytic NH3 oxidation to N2 under mild conditions is a promising strategy. However, developing visible light photocatalysts for NH3 oxidation is still in its infancy. Here, we fabricate N-TiO2 and Ag/AgCl/N-TiO2 photocatalysts by sol-gel and photodeposition methods, respectively. The introduction of N not only endows TiO2 with visible light response (absorption edge at 460 nm) but also results in the formation of heterophase junction (anatase and rutile). Thus, N-TiO2 shows 2.0 and 1.8 times higher than those over anatase TiO2 and commercial TiO2 for NH3 oxidation under full spectrum irradiation. Meanwhile, surface modification of Ag can simultaneously enhance visible light absorption (generating localized surface plasmon resonance effect) and charge separation efficiency. Therefore, the photocatalytic activity of Ag/AgCl/N-TiO2 is further improved. Furthermore, the presence of N and Ag also enhances the selectivity of N2 product owing to the change of reaction pathway. This work simultaneously regulates photocatalytic conversion efficiency and product selectivity, providing some guidance for developing highly efficient photocatalysts for NH3 elimination.

Prevalence and characteristics of comorbid stroke and traumatic brain injury in a real-world population: findings from a nationally representative cross-sectional survey in China.

BACKGROUND: In China, data on the prevalence and characteristics of comorbid stroke and traumatic brain injury (TBI) in real-world populations are still lacking but of paramount importance for the evidence-based prevention and control of the comorbidity of the two diseases. This study aimed to investigate the prevalence and characteristics of comorbid stroke and TBI in a real-world population. METHODS: In 2013, a nationally representative, door-to-door survey on stroke and TBI using a complex, multistage, probability sampling design was conducted among approximately 600,000 participants from 155 urban and rural areas in China (Ethic ID: KY2013-006-01). The weighted prevalence of comorbid stroke and TBI was estimated using individuals' final weight. A Poisson regression analysis was used to compare the rate ratio of the comorbidity prevalence among different subgroups of the population, including age, sex, place of residence, and geographic location subgroups. For analyses of associations between the comorbidities and predictors of interest, all other variables were adjusted for in a multinomial logistic regression model. RESULTS: Among the 596,536 people, 219 patients with comorbid stroke and TBI were identified. The point prevalence of comorbid stroke and TBI weighted to the China 2010 census population was 29.30 (95% CI: 22.69-37.84) per 100,000 population in China. The adjusted prevalence of post-TBI stroke in patients with previous TBI was significantly higher than that of post-stroke TBI in patients with previous stroke (6021.3 vs. 811.1 per 100,000 people; rate ratio: 11.001; 95% CI: 8.069-14.998). Patients with nonconcussion had significantly higher rates of both pre-stroke TBI (odds ratio: 4.694; 95% CI: 3.296-6.687) and post-stroke TBI (odds ratio: 6.735; 95% CI: 3.719-12.194) than patients with concussion. Compared to patients with ischaemic stroke, patients with subarachnoid haemorrhage (odds ratio: 2.044; 95% CI: 1.097-3.809) and intracerebral haemorrhage (odds ratio: 1.903; 95% CI: 1.296-2.795) had significantly higher rates of post-TBI stroke. CONCLUSIONS: The high prevalence of stroke among TBI patients is becoming a new public health issue. TBI patients, especially those with nonconcussion TBI, are more likely to develop comorbid stroke and TBI than stroke patients, especially ischaemic stroke patients.

Mortality due to primary brain tumours in China and detection rate in people with suspected symptoms: a nationally representative cross-sectional survey.

BACKGROUND AND PURPOSE: Epidemiological data on primary brain tumours (PBTs) are lacking due to the difficulty in case ascertainment among the population. Thus, we aimed to estimate mortality due to PBTs in China nationwide and the detection rate in people with suspected symptoms. METHODS: A multistage, complex sampling survey regarding mortality due to PBTs in Chinese individuals was carried out by reviewing all causes of death within a year. The detection rates in people with suspected symptoms were estimated based on PBT symptom screening and neurologist reviews and compared between groups by logistic regression analysis. RESULTS: Weighted mortality due to PBT was 1.6 (0.8-3.3) per 100,000 population in Chinese individuals, 1.8 (0.7-4.6) per 100,000 population in men, and 1.5 (0.5-4.5) per 100,000 population in women. Among 14,990 people with suspected symptoms, the PBT detection rate was 306.9 (95% CI 224.7-409.3) per 100,000 population in the total population, 233.0 (95% CI 135.7-373.1) per 100,000 population in men, and 376.9 (95% CI 252.4-546.3) per 100,000 population in women. People with an unsteady gait (OR 2.46; 95% CI 1.09-5.51; P=0.029), visual anomalies (3.84; 1.88-7.85; P<0.001), and headache (2.06; 1.10-3.86; P=0.023) were more likely to have a brain tumour than those without corresponding symptoms, while people with dizziness/vertigo were less likely to have a brain tumour than those without corresponding symptoms (0.45; 0.23-0.87; P=0.017). CONCLUSIONS: Mortality due to PBT in China was low, with a nationwide estimate of 21,215 (10,427-43,165) deaths attributable to PBTs annually. However, the detection rate of PBTs can be greatly improved based on symptom screening in the population.

Ischemic stroke is associated with the pro-inflammatory potential of N-glycosylated immunoglobulin G.

BACKGROUND: Glycosylation significantly affects protein structure and function and thus participates in multiple physiologic and pathologic processes. Studies demonstrated that immunoglobulin G (IgG) N-glycosylation associates with the risk factors of ischemic stroke (IS), such as aging, obesity, dyslipidemia, type 2 diabetes, and hypertension. METHODS: The study aimed to investigate the association between IgG N-glycosylation and IS in a Chinese population. IgG glycome composition in patients with IS (n = 78) and cerebral arterial stenosis (CAS) (n = 75) and controls (n = 77) were analyzed by ultra-performance liquid chromatography. RESULTS: Eleven initial glycans and 10 derived glycans in IgG glycome representing galactosylation, sialylation, and bisecting GlcNAc significantly differed between IS patients and CAS and healthy controls after controlling for gender, age, obesity, diabetes, hypertension, and dyslipidemia. Logistic regression models incorporating IgG glycan traits were able to distinguish IS from CAS (area under receiver-operator characteristic curves (AUC), 0.802; 95% confidence interval (CI), 0.732-0.872) and controls (AUC, 0.740; 95% CI, 0.661-0.819). The canonical correlation analysis indicated that initial N-glycan structures are significantly correlated with inflammation markers (r = 0.566, p < 0.001). CONCLUSION: Our findings indicated that loss of galactose and sialic acid, as well as addition of bisecting GlcNAc, might involve in pro- or anti-inflammatory IgG functionality and further contribute to the pathogenesis of IS. IgG glycan profiles may be developed as clinical useful biomarkers for chronic disease in the future.

The changes of immunoglobulin G N-glycosylation in blood lipids and dyslipidaemia.

BACKGROUND: Alternative N-glycosylation has significant structural and functional consequences on immunoglobulin G (IgG) and can affect immune responses, acting as a switch between pro- and anti-inflammatory IgG functionality. Studies have demonstrated that IgG N-glycosylation is associated with ageing, body mass index, type 2 diabetes and hypertension. METHODS: Herein, we have demonstrated patterns of IgG glycosylation that are associated with blood lipids in a cross-sectional study including 598 Han Chinese aged 20-68 years. The IgG glycome composition was analysed by ultra-performance liquid chromatography. RESULTS: Blood lipids were positively correlated with glycan peak GP6, whereas they were negatively correlated with GP18 (P < 0.05/57). The canonical correlation analysis indicated that initial N-glycan structures, including GP4, GP6, GP9-12, GP14, GP17, GP18 and GP23, were significantly correlated with blood lipids, including total cholesterol, total triglycerides (TG) and low-density lipoprotein (r = 0.390, P < 0.001). IgG glycans patterns were able to distinguish patients with dyslipidaemia from the controls, with an area under the curve of 0.692 (95% confidence interval 0.644-0.740). CONCLUSIONS: Our findings indicated that a possible association between blood lipids and the observed loss of galactose and sialic acid, as well as the addition of bisecting GlcNAcs, which might be related to the chronic inflammation accompanying with the development and procession of dyslipidaemia.

The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CAPN10, APM1 and FUT6 genes.

Genome-wide association studies have successfully identified over 70 loci associated with the risk of type 2 diabetes mellitus (T2DM) in multiple populations of European ancestry. However, the risk attributable to an individual variant is modest and does not yet provide convincing evidence for clinical utility. Association between these established genetic variants and T2DM in general populations is hitherto understudied in the isolated populations, such as the Uyghurs, resident in Hetian, far southern Xinjiang Uyghur Autonomous Region, China. In this case-control study, we genotyped 13 single-nucleotide polymorphisms (SNPs) at 10 genes associated with diabetes in 130 cases with T2DM and 135 healthy controls of Uyghur, a Chinese minority ethnic group. Three of the 13 SNPs demonstrated significant association with T2DM in the Uyghur population. There were significant differences between the T2DM patients and controls in the risk allele distributions of rs3792267 (CAPN10) (P = 0.002), rs1501299 (APM1) (P = 0.017), and rs3760776 (FUT6) (P = 0.031). Allelic carriers of rs3792267-A, rs1501299-T, and rs3760776-T had a 2.24-fold [OR (95% CI): 1.35-3.71], 0.59-fold [OR (95% CI): 0.39-0.91], 0.57-fold [OR (95% CI): 0.34-0.95] increased risk for T2DM respectively. We further confirmed that the cumulative risk allelic scores calculated from the 13 susceptibility loci for T2DM differed significantly between the T2DM patients and controls (P = 0.001), and the effect of obesity/overweight on T2DM was only observed in the subjects with a combined risk allelic score under a value of 17. This study observed that the SNPs rs3792267 in CAPN10, rs1501299 in APM1, and rs3760776 in FUT6 might serve as potential susceptible biomarkers for T2DM in Uyghurs. The cumulative risk allelic scores of multiple loci with modest individual effects are also significant risk factors in Uyghurs for T2DM, particularly among non-obese individuals. This is the first investigation having observed/found genetic variations on genetic loci functionally linked with glycosylation associated with the risk of T2DM in a Uyghur population.

China suboptimal health cohort study: rationale, design and baseline characteristics.

BACKGROUND: Suboptimal health status (SHS) is a physical state between health and disease, characterized by the perception of health complaints, general weakness, chronic fatigue and low energy levels. SHS is proposed by the ancient concept of traditional Chinese medicine (TCM) from the perspective of preservative, predictive and personalized (precision) medicine. We previously created the suboptimal health status questionnaire 25 (SHSQ-25), a novel instrument to measure SHS, validated in various populations. SHSQ-25 thus affords a window of opportunity for early detection and intervention, contributing to the reduction of chronic disease burdens. METHODS/DESIGN: To investigate the causative effect of SHS in non-communicable chronic diseases (NCD), we initiated the China suboptimal health cohort study (COACS), a longitudinal study starting from 2013. Phase I of the study involved a cross-sectional survey aimed at identifying the risk/protective factors associated with SHS; and Phase II: a longitudinal yearly follow-up study investigating how SHS contributes to the incidence and pattern of NCD. RESULTS: (1) Cross-sectional survey: in total, 4313 participants (53.8 % women) aged from 18 to 65 years were included in the cohort. The prevalence of SHS was 9.0 % using SHS score of 35 as threshold. Women showed a significantly higher prevalence of SHS (10.6 % in the female vs. 7.2 % in the male, P < 0.001). Risk factors for chronic diseases such as socioeconomic status, marital status, highest education completed, physical activity, salt intake, blood pressure and triglycerides differed significantly between subjects of SHS (SHS score ≥35) and those of ideal health (SHS score <35). (2) Follow up: the primary and secondary outcomes will be monitored from 2015 to 2024. CONCLUSIONS: The sex-specific difference in prevalence of SHS might partly explain the gender difference of incidence of certain chronic diseases. The COACS will enable a thorough characterization of SHS and establish a cohort that will be used for longitudinal analyses of the interaction between the genetic, lifestyle and environmental factors that contribute to the onset and etiology of targeted chronic diseases. The study together with the designed prospective cohort provides a chance to characterize and evaluate the effect of SHS systemically, and it thus generates an unprecedented opportunity for the early detection and prevention of chronic disease.

Causal Relationship Between Micronutrient and Sleep Disorder: A Mendelian Randomization Study.

Background: Sleep played an important part in human health, and COVID-19 led to a continuous deterioration of sleep. However, the causal relationship between micronutrient and sleep disorder was not yet fully understood. Methods: In this research, the genetic causal relationship between micronutrient and sleep disorder was analyzed utilizing a two-sample Mendelian randomization (MR). Single nucleotide polymorphisms (SNPs) were used as instrumental variables. The analyses were conducted using the MR-Egger, inverse variance weighted, weighted mode, weighted median, simple mode, Cochran's Q test and leave-one-out. Results: Our results suggested that 8 genetically predicted micronutrients participated in sleep disorders, including liver iron (L-iron) and iron in sleeping too much, spleen iron (S-iron) in sleeplessness/insomnia, trouble falling or staying asleep, sleep duration (undersleepers) and nonorganic sleeping disorders, iron metabolism disorder (IMD) and vitamin B12 deficiency anaemia (VB12DA) in narcolepsy, urine sodium (uNa) in narcolepsy, sleep apnea syndrome and sleep disorder, vitamin D (VD) in sleep duration (oversleepers), 25-Hydroxyvitamin D (25(OH)D) in trouble falling or staying asleep. Conclusion: Our study used Mendelian randomization methods at the SNP level to explore the potential causal relationship among L-iron, iron, S-iron, IMD, uNa, 25(OH)D, VD, VB12DA with certain sleep disorder subtypes. Our results uncovered a micronutrient-based strategy for alleviating sleep disorder symptoms.

The interplay between cytokines and stroke: a bi-directional Mendelian randomization study.

Stroke, the second leading cause of death and disability, causes massive cell death in the brain followed by secondary inflammatory injury initiated by disease associated molecular patterns released from dead cells. Nonetheless, the evidence regarding the causal relationship between inflammatory cytokines and stroke subtypes is obscure. To leverage large scale genetic association data to investigate the interplay between circulating cytokines and stroke, we adopted a two-sample bi-directional Mendelian randomization (MR) analysis. Firstly, we performed a forward MR analysis to examine the associations of genetically determined 31 cytokines with 6 stroke subtypes. Secondly, we conducted a reverse MR analysis to check the associations of 6 stroke subtypes with 31 cytokines. In the forward MR analysis, genetic evidence suggests that 21 cytokines were significantly associated with certain stroke subtype risk with |ß| ranging from 1.90 × 10-4 to 0.74. In the reverse MR analysis, our results found that five stroke subtypes (intracerebral hemorrhage (ICH), large artery atherosclerosis ischemic stroke (LAAS), lacunar stroke (LS), cardioembolic ischemic stroke (CEI), small-vessel ischemic stroke (SV)) caused significantly changes in 16 cytokines with |ß| ranging from 1.08 × 10-4 to 0.69. In particular, those five stroke subtypes were statistically significantly associated with C-reactive protein (CRP). In addition, ICH, LAAS, LS and SV were significantly correlated with vascular endothelial growth factor (VEGF), while LAAS, LS, CEI and SV were significantly related to fibroblast growth factor (FGF). Moreover, integrated bi-directional MR analysis, these factors (IL-3Rα, IL-6R, IL-6Rα, IL-1Ra, insulin-like growth factor-1(IGF-1), IL-12Rß2) can be used as predictors of some specific stroke subtypes. As well as, IL-16 and C-C motif chemokine receptor 7 (CCR7) can be used as prognostic factors of stroke. Our findings prognostic identify potential pharmacological opportunities, including perturbation of circulating cytokines for both predicting stroke risk and post stroke treatment effects. As we conducted a comprehensive search and analysis of stroke subtype and cytokines in the existing publicly available GWAS database, the results have good population-generalizability.

Needs and views on healthy lifestyles for the prevention of dementia and the potential role for mobile health (mHealth) interventions in China: a qualitative study.

OBJECTIVES: Over the coming decades, China is expected to face the largest worldwide increase in dementia incidence. Mobile health (mHealth) may improve the accessibility of dementia prevention strategies, targeting lifestyle-related risk factors. Our aim is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, supporting the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study. DESIGN: Qualitative semi-structured interview study, using thematic analysis. SETTING: Primary and secondary care in Beijing and Tai'an, China. PARTICIPANTS: Older adults aged 55 and over without dementia with an increased dementia risk, possessing a smartphone. Participants were recruited through seven hospitals participating in the PRODEMOS study, purposively sampled on age, sex, living area and history of CVD and diabetes. RESULTS: We performed 26 interviews with participants aged 55-86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese lifestyle practices as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the care burden put on family members. However, time-consuming family obligations and other social values could also impede healthy behaviours such as regular physical activity. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional. CONCLUSIONS: The Chinese older adults included in this study highly value a healthy lifestyle. They express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for dementia and CVD. TRIAL REGISTRATION NUMBER: ISRCTN15986016; Pre-results.

Prevalence, Incidence, and External Causes of Traumatic Spinal Cord Injury in China: A Nationally Representative Cross-Sectional Survey.

BACKGROUND AND PURPOSE: The epidemiological characteristics of traumatic spinal cord injury (TSCI) in China are unclear. Thus, we aimed to study prevalence, incidence, and external causes of TSCI in China nationwide. METHODS: In 2013, we conducted a nationally representative, door-to-door epidemiological survey on TSCI in China using a complex, multistage, probability sampling design. RESULTS: In China, the point prevalence of TSCI standardized to the China census population 2010 was 569.7 (95% CI: 514.2-630.4) per 1,000,000 in the population, 753.6 (95% CI: 663.3-854.3) per 1,000,000 among men, and 387.7 (95% CI: 324.8-461.1) per 1,000,000 among women. The incidence of TSCI standardized to the China census population 2010 was 49.8 (95% CI: 34.4-70.7) per 1,000,000 per year in the population, 63.2 (95% CI: 38.9-98.5) per 1,000,000 among men, and 36.9 (95% CI: 19.5-65.9) per 1,000,000 among women. Among the 415 TSCI events in 394 prevalent cases, the top three injury causes were falls (55.2%), motor vehicle collisions (MVCs) (26.5%), and strike injuries (10.1%), while other injury causes including gunshot and explosion accounted for 8.2%. Among the 394 prevalent cases, the mean age of patients at the time of injury was 43.7 ± 17.1 years; the male-to-female ratio was 1.86:1. CONCLUSION: It is estimated that there are 759,302 prevalent patients with TSCI in total and 66,374 new TSCI cases annually in China. Falls and MVCs are still 2 major external causes for TSCI in China.

Annual rates of and factors influencing inpatient and outpatient transient ischaemic attacks in Chinese population: a nationally representative cross-sectional survey.

OBJECTIVES: To investigate the rates and influencing factors of transient ischaemic attack (TIA) inpatient admissions and outpatient visits in China. SETTING: A door-to-door survey of 178 059 families from 155 urban and rural areas in 31 provinces in China, 2013. PARTICIPANTS: Total 596 536 people were assessed in the annual rate analysis, and 829 TIA patients were assessed in the influencing factor analysis. MAIN OUTCOME MEASURES: The weighted annual rates of TIA inpatient admissions and outpatient visits and the factors influencing inpatient admissions and outpatient visits for TIA patients. RESULTS: The weighted annual inpatient admission rate per TIA patient was 25.8 (95% CI: 18.4 to 36.2) per 100 000 in the population, whereas the weighted annual inpatient admission rate for patients with TIAs was 32.5 (95% CI: 23.3 to 38.9) per 100 000 in the population. The weighted annual outpatient visit rate per TIA patient was 34.4 (95% CI: 26.2 to 45.1) per 100 000 in the population, whereas the weighted annual outpatient visit rate for patients with TIAs was 149.6 (95% CI: 127.0 to 165.5) per 100 000. The inpatient rate was higher for men than for women (OR: 2.24; 95% CI: 1.40 to 3.59; p=0.001), for TIA patients with stroke than for patients with isolated TIAs (2.93; 2.01 to 4.25; p<0.001), for TIA patients with hypertension than for TIA patients without hypertension (2.60; 1.65 to 4.11; p<0.001). The outpatient rate was higher for TIA patients with stroke than for patients with isolated TIAs (1.88; 1.33 to 2.64; p<0.001), for TIA patients with dyslipidaemia than for TIA patients without dyslipidaemia (1.92; 1.30 to 2.83; p=0.001). CONCLUSIONS: The annual rates of TIA inpatient admissions and outpatient visits in population are low, probably due to the lack of access to inpatient and outpatient services experienced by the majority of TIA patients in the population, and individuals' socio-demographic characteristics, disease histories and stroke prognosis may be associated with inpatient and outpatient TIAs.

Jidong cognitive impairment cohort study: objectives, design, and baseline screening.

The risk of dementia increases in patients with cognitive impairment. However, it is not clear what factors contribute to the onset of dementia in those with cognitive impairment. In this prospective cohort study, we will investigate the every-five-year incidence of cognitive impairment and prognostic factors for cognitive impairment. The Jidong cognitive impairment cohort was established from April 2012 to August 2015, during which we recruited 5854 healthy participants (55.1% male) older than 45 years (mean, 57 years). Participants received a health examination in the Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation. Baseline data and blood samples were collected. Cognitive impairment was evaluated using the Mini-Mental State Examination, and was defined as a Mini-Mental State Examination score of less than 24. Dementia was assessed using the criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth edition), the International Working Group criteria, and the Mini-Mental State Examination score. The follow-up will continue until December 2024, during which a prognostic model will be constructed. The primary outcome is the presence/absence of dementia and the secondary outcome is quality of life. Baseline screening results showed the following: (1) Cognitive impairment was apparent in 320 participants (5.5%). These participants will be excluded from the Jidong cohort study, and the remaining participants will be followed up. (2) Of the 320 participants with cognitive impairment, there was a significantly higher prevalence of illiteracy than other education levels (35.9%, P < 0.05). Age, arterial hypertension, alcohol consumption, and passive smoking differed significantly between the cognitive impairment and healthy groups (P < 0.05). Multivariate logistic regression models showed that age (odds ratio [OR] = 1.059, 95% confidence interval [CI]: 1.044-1.074) and arterial hypertension (OR = 1.665, 95% CI: 1.143-2.427) were risk factors for mild cognitive impairment. With the increase of educational level (illiteracy, primary school, junior high school, high school, university, and above), cognitive impairment gradually decreased (OR < 1, P < 0.05). (3) This cohort study has initially screened for several risk factors for cognitive impairment at baseline, and subsequent prospective data will further describe, validate, and evaluate the effects of these risk factors on cognitive impairment and dementia. These results can provide clinical evidence for the early prevention of cognitive impairment and dementia. The study was approved by the Ethics Committee of Kailuan General Hospital of Tangshan City and the Medical Ethics Committee, Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation on July 12, 2013 (approval No. 2013 YILUNZI 1).

Causal association of circulating cholesterol levels with dementia: a mendelian randomization meta-analysis.

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 < 0.01), whereas carriers of ε4 allele were of increased risk of AD (OR = 3.62; 95% CI: 3.03-4.32; P < 0.05), compared to these of ε3 allele. Circulating TC was significantly reduced in carriers of ε2 allele (WMD = - 0.29 mmol/L; 95% CI: -0.54 to -0.03; P < 0.05) and increased in carriers of ε4 allele (WMD = 0.42 mmol/l; 95% CI: 0.001-0.84; P < 0.05). In addition, carriers of ε4 allele had reduction in circulating HDL-C (WMD = - 0.04 mmol/L; 95% CI: - 0.07 to -0.001; P < 0.05). In comparing allele ε2 with ε3, the predicted OR of having AD for 1 mg/dL increment in circulating TC was 0.97 (95% CI: 0.86-0.98; P < 0.05). Comparing allele ε4 with ε3, the predicted OR for a 1 mg/dL increment in TC was 1.08 (95% CI: 1.05-17.58; P < 0.05), and reduction in HDL-C was 2.30 (95% CI: 1.51-43.99; P < 0.05). Our findings demonstrate that high circulating TC and reduced HDL-C levels might be potential risk factors of the development of AD.

Modelling biological age based on plasma peptides in Han Chinese adults.

Age-related disease burdens increased over time, and whether plasma peptides can be used to accurately predict age in order to explain the variation in biological indicators remains inadequately understood. Here we first developed a biological age model based on plasma peptides in 1890 Chinese Han adults. Based on mass spectrometry, 84 peptides were detected with masses in the range of 0.6-10.0 kDa, and 13 of these peptides were identified as known amino acid sequences. Five of these thirteen plasma peptides, including fragments of apolipoprotein A-I (m/z 2883.99), fibrinogen alpha chain (m/z 3060.13), complement C3 (m/z 2190.59), complement C4-A (m/z 1898.21), and breast cancer type 2 susceptibility protein (m/z 1607.84) were finally included in the final model by performing a multivariate linear regression with stepwise selection. This biological age model accounted for 72.3% of the variation in chronological age. Furthermore, the linear correlation between the actual age and biological age was 0.851 (95% confidence interval: 0.836-0.864) and 0.842 (95% confidence interval: 0.810-0.869) in the training and validation sets, respectively. The biological age based on plasma peptides has potential positive effects on primary prevention, and its biological meaning warrants further investigation.

GeographicalDifference, Rural-urban Transition and Trend in Stroke Prevalence in China: Findings from a National Epidemiological Survey of Stroke in China.

Accurate and up-to-date provincial and regional-level stroke prevalence estimates are important for research planning and targeted strategies for stroke prevention and management. However, recent and comprehensive evaluation is lacking over the past 30 years in China. This study aimed to examine the geographical variations in stroke prevalence based on data from the National Epidemiological Survey of Stroke in China (NESS-China) and demonstrate urban-rural transition and trend over three decades. The stroke prevalence (prevalence day, August 31, 2013) was estimated using the world standard population. The stroke prevalence was 873.4 per 100,000 population, and varied from 218.0 in Sichuan to 1768.9 in Heilongjiang. Stroke prevalence exhibited a noticeable north-south gradient (1097.1, 917.7, and 619.4 in the north, middle, and the south, respectively; P < 0.001) and showed a 2.0-fold, 1.5-fold, and 1.2-fold increase in rural areas in the north, the middle, and the south, respectively, from 1985 to 2013. Overall, stroke prevalence was higher in the rural regions than in the urban (945.4 versus 797.5, P < 0.001) regions. However, the converse was depicted in 12 provinces. A noticeable geographical variation in stroke prevalence was observed and was evolving overtime in China. It is imperative that effective public health policies and interventions be implemented, especially in those regions with higher prevalence.

Suboptimal health status as an independent risk factor for type 2 diabetes mellitus in a community-based cohort: the China suboptimal health cohort study.

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.