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The purpose of this study is to investigate whether the mitochondrial DNA (mtDNA) content can reflect the state of mosaic embryos.The study included 1669 blastocysts derived from 394 PGT-A cycles between January 2018 and December 2020, in which preimplantation genetic testing for aneuploidy was performed and mtDNA content was determined. The standard deviation (SD) of whole genomic sequencing data was calculated for quality control. mtDNA content was measured as the proportion of mtDNA to genomic DNA. 1558 blastocysts with SD values less than 4.0 and mtDNA values less than 0.4% were selected for statistical analysis.The mtDNA content of the PGT mosaic group was significantly higher than that of the PGT normal group (P 0.001). Twenty-six mosaic embryos were transferred, and the results were as follows: 2 out of 26 had undergone a spontaneous miscarriage, 15 were not pregnant, and 9 resulted in a live birth. There were significant differences in the mtDNA content between the miscarriage/non-pregnancy group and the live birth group (**P 0.01; ***P 0.001). There was no mosaic embryo with more than 0.157% mtDNA content found in the live birth group.This study demonstrates that mtDNA analysis has the ability to identify mosaic embryos with high developmental potential. It can be a valuable supplementary index for the selection of mosaic embryos for transfer. Larger studies with a greater sample size will further our understanding of the relationships between metabolic activity and mosaicism.

Cognitive impairment after stroke/transient ischemic attack (TIA) has a high prevalence. The authors aimed to explore the risk factors for declined cognitive function with Montreal Cognitive Assessment (MoCA)-Beijing in patients with stroke/TIA at acute phase. Total 2283 patients with acute stroke/TIA without a history of dementia were assessed at 2 weeks of onset. Patients were assessed by MoCA-Beijing on day 14 and at 3 months follow-ups. Cognitive impairment was defined as MoCA-Beijing ≤22. Patients' cognitive status was considered as declined if there were a reduction of ≥2 points in MoCA-Beijing score and patients were considered to have improved if there were an increase of ≥2 points. The score of MoCA-Beijing was considered to be stable if there were an increase or decrease of 1 point. Most patients were in 60 s (60.96 ± 10.75 years old) with a median (interquartile range) National Institute of Health Stroke Scale score of 3.00 (4.00) and greater than primary school level of education, and 1657 participants (72.58%) were male. Cognitive evaluation was conducted in 2283 of 2625 patients (82.70%) with MoCA-Beijing at baseline. Total 292 (12.79%) patients have a cognitive decline at 3 months, 786 (34.42%) patients were stable and 1205 (52.78%) patients were improved. In the logistic regression, a history of hypertension was associated with cognitive deterioration from baseline to 3-month. Patients with a history of hypertension have a higher risk for cognitive deterioration from baseline to 3-month after stroke/TIA.

This study examined the associations of fine particulate matter (PM

This study was undertaken to identify the risk of bleeding events and potential risk factors within 90 days in patients who carried CYP2C19 loss-of-function alleles and received dual antiplatelet therapy after minor stroke or transient ischemic attack.A total of 6,412 patients were enrolled from the CHANCE-2 (Clopidogrel with Aspirin in High-Risk Patients with Acute Non-disabling Cerebrovascular Events II) trial. The main outcome was any bleeding within 90 days defined by the criteria from GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries).A total of 250 (3.9%) bleeding events were reported, which occurred mainly within the 21 days of dual antiplatelet therapy (200 cases, 3.1%). Minor bleeding of the skin bruises, epistaxis, and gum bleeding were most frequent. Multivariate analysis showed that treatment with ticagrelor-aspirin compared with clopidogrel-aspirin was associated with increased bleeding (hazard ratio [HR] = 2.21, 95% confidence interval [CI] = 1.68-2.89, p 0.001). Current smoking was associated with a lower risk of bleeding (HR = 0.70, 95% CI = 0.52-0.95, p = 0.02). Additionally, ticagrelor-aspirin compared with clopidogrel-aspirin was associated with higher risk of bleeding in patients aged65 years (HR = 2.87, 95% CI = 1.95-4.22) and those without diabetes mellitus (HR = 2.65, 95% CI = 1.88-3.73; p for interaction = 0.04 and 0.03, respectively).Bleeding events mostly occurred within the 21-day dual antiplatelet therapy stage and were generally mild. The risk of bleeding was greater in nonsmoking patients, and was associated with treatment with ticagrelor-aspirin compared with clopidogrel-aspirin, particularly in patients aged65 years and nondiabetic patients. ANN NEUROL 2022;91:380-388.

Background/Aims: Data about the independent and combined effects of cystatin C-based estimated glomerular filtration rate (eGFRcys) and albuminuria on the risk of poor outcome in stroke patients are limited. The aim was to elucidate how these two renal markers affect the clinical outcomes after ischemic stroke separately and jointly. Methods: The study subjects consisted of 10,197 patients with ischemic stroke from the third China National Stroke Registry. The study outcomes were all-cause mortality, poststroke disability, recurrence of stroke, and cardiocerebral vascular disease (CVD) composite events. Cox proportional hazard models and multivariable logistic regression model were applied to evaluate the effects of eGFRcys and urine albumin-creatinine ratio (ACR) on these outcomes. Results: Both reduced eGFRcys and increased ACR were independently associated with higher incidences of all-cause death and poststroke disability (p < 0.01). Mildly decreased eGFRcys (60–89 mL/min/1.73 m2) is associated with increased risk of all-cause death and poststroke disability in the presence of high-normal ACR (10–29 mg/g). Patients with both eGFRcys 2 and ACR ≥30 mg/g at baseline had a 6.8-fold risk for all-cause mortality and 3.6-fold risk for poststroke disability, compared with patients with eGFRcys of 90–119 mL/min/1.73 m2 and ACR cys showed no relationship with these outcomes. Conclusions: Both decreased eGFRcys and albuminuria are independent risk factors for all-cause death and poststroke disability. Combining the two markers is useful for improving risk stratification even in those without chronic kidney disease.

Background and Objectives: To investigate the relationship between homocysteine levels and post-stroke cognitive impairment (PSCI) in Chinese female and male populations with minor acute ischemic stroke or transient ischemic attack. Materials and methods: A total of 1070 participants with clinically confirmed acute minor ischemic stroke or transient ischemic attack and baseline homocysteine information from a nationwide multicenter prospective registry study in China were included in this study. Of these, 919 patients had cognitive assessments at 3-month follow-ups and 584 participants had cognitive assessments at 12-month follow-ups. The incidence of PSCI was defined as a Montreal Cognitive Assessment score ≤22. The differences in homocysteine levels and the incidence of PSCI were compared between female and male populations. Relationships between homocysteine levels and the incidence of PSCI in female and male populations were analyzed using multiple logistic regression, respectively. Results: Females had lower baseline homocysteine levels than males. Compared to males, females had lower education levels, lower rates of smoking and alcohol intake, and higher rates of diabetes and hypertension. No relationship was observed between elevated homocysteine level and 3-month PSCI incidence in either females or males. After adjusting the confounders, elevated baseline homocysteine significantly increased the 12-month PSCI risk (odds ratio 3.28, 95% confidence interval 1.47–7.34, P = 0.004) in females, but not in males (odds ratio 0.86, 95% confidence interval 0.49–1.49, P = 0.586). Conclusion: Elevated homocysteine levels increased the 12-month PSCI risk in females, but not in males with minor acute ischemic stroke or transient ischemic attack.

Background and Purpose: It is still unclear whether the residual cholesterol and inflammatory risk in the acute phase is associated with prognosis of stroke. We aimed to investigate the proportion and relative contribution of residual cholesterol and inflammatory risk, determined by baseline low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) levels, to the risk of recurrent stroke and poor functional outcome at 1 year. Methods: In this prospective multicenter cohort study, 10 499 consecutive acute ischemic stroke and transient ischemic attack patients with levels of LDL-C and hsCRP were enrolled. Patients were divided into 4 groups: residual cholesterol risk only (LDL-C ≥2.6 mmol/L and hsCRP Results: The relative proportions of patients with RIR only, residual cholesterol risk only, both risk, and neither were 21.3%, 23.7%, 14.4%, and 40.6%, respectively. RIR only was independently associated with recurrent stroke (adjusted hazard ratio, 1.18 [95% CI, 1.00–1.40]; P =0.05). The association was slightly attenuated after further adjusting for usage of antiplatelet agent and statin during 1-year follow-up in addition to the traditional risk factors (hazard ratio, 1.31 [95% CI, 0.99–1.76]; P =0.07). When applying the LDL-C cutoff value of 1.8 mmol/L in the sensitivity analyses, such association in large-artery atherosclerosis subtype was more significant (adjusted hazard ratio, 1.69 [95% CI, 1.06–2.67]; P =0.03). Patients with RIR only also had increased risk of poor functional outcome (adjusted odds ratio, 1.43 [95% CI, 1.24–1.64]; P Conclusions: In the patients with acute ischemic stroke or transient ischemic attack, RIR only could be predictive for recurrent stroke, especially for those with large-artery atherosclerosis, and poor functional outcome.

Background Insulin resistance is an important cause of cardiovascular events and cerebral infarction development. We aimed to investigate the association of the triglyceride glucose (TyG) index with atherosclerotic burden and plaques in coronary, intra- and extracranial arteries in participants with non-diabetes, and compared the results with that of the homeostasis model assessment of insulin resistance (HOMA-IR). Methods Participants without diabetes in the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were included. We categorized participants by tertiles of the TyG index and the concordance/discordance of the TyG index and HOMA-IR. Discordance was defined as a TyG index equal to or greater than the median and HOMA-IR less than the median, or vice versa. The atherosclerosis plaques and burden in coronary, intra- and extracranial arteries were evaluated. The association of HOMA-IR and TyG index with the presence of atherosclerotic plaques and atherosclerotic burden was assessed by binary and ordinal logistic regression models, respectively. Results Among 2,719 included participants, the average age was 60.9 (± 6.6) years, and 53.0% were female. Both TyG index and HOMA-IR were associated with increased odds of coronary/intra- and extracranial atherosclerotic plaques and burden after adjustment for age, sex, currenting smoking and drinking (all P Conclusion Elevated TyG index was associated with increased odds of atherosclerosis in coronary/intra- and extracranial arteries. Compared with HOMA-IR, the TyG index was more strongly associated with intracranial atherosclerosis. Moreover, discordantly high TyG index with HOMA-IR was also important for atherosclerosis identification.

Introduction: The association between the changes in albuminuria levels and the clinical prognosis of stroke is unknown. The present study aimed to explore the relationships between changes in albuminuria and the risk of adverse stroke outcomes. Methods: The patients with ischemic stroke or transient ischemic attack from the Third China National Stroke Registry (CNSR-III) who had the urinary albumin-to-creatinine ratio (ACR) detected at baseline and 3-month were recruited. They were classified into 4 groups according to baseline and 3-month ACR and followed up for 1 year. Results: A total of 5,311 patients were finally included in the study. There were 3,738 (70.4%), 483 (9.1%), 451 (8.5%), and 639 (12.0%) patients with no albuminuria, baseline albuminuria, 3-month albuminuria, and persistent albuminuria, respectively. After adjustment for confounding variables, persistent albuminuria was independently associated with all-cause death (hazard ratio [HR], 2.23; 95% CI, 1.17–4.25; p = 0.02), stroke recurrence (HR, 1.55; 95% CI, 1.02–2.36; p = 0.04), and poor functional outcome (OR, 2.22; 95% CI, 1.66–2.96; p < 0.001). Baseline albuminuria was independently associated with poor functional outcome (OR, 1.65; 95% CI, 1.19–2.28; p = 0.003), while 3-month albuminuria was independently associated with stroke recurrence (HR, 1.68; 95% CI, 1.06–2.65; p = 0.03). Conclusions: Changes in albuminuria can predict adverse 1-year outcomes in Chinese ischemic stroke patients. In particular, persistent albuminuria was independently associated with 1-year all-cause death, stroke recurrence, and poor functional outcome.

Diabetes mellitus is a strong independent risk factor for stroke recurrence. However, the association between diabetes duration and the prognosis of stroke remains uncertain. We aimed to characterize whether an association exists between diabetes duration and stroke outcomes in patients with ischemic stroke or transient ischemic attack (TIA).Between 2015 and 2018, 14,674 patients with ischemic stroke or TIA within 7 days and older than 18 years from the Third China National Stroke Registry (CNSR-III) were included in this analysis. Diabetes duration at baseline was collected by face-to-face interviews and further categorized into groups of without diabetes, diabetes 4, 4 to 8 and ≥8 years. The association between diabetes duration and clinical outcomes, including stroke recurrence, poor function outcome (modified Rankin Scale score of 3-6), and all-cause mortality at the 1-year follow-up after stroke onset, was evaluated by a multivariable Cox proportional hazard regression model, competing risk model and logistic regression model with adjustment for demographic and clinical features.Among the 14,674 patients included, the average age was 62.0 years, and 68.5% were male. There were 1419 (9.7%) patients who had stroke recurrence, 1912 (13.0%) who had poor function outcome, and 478 (3.3%) who had all-cause mortality at the 1-year follow-up. After adjusting for potential covariates, a diabetes duration ≥8 years was associated with an increased risk of 1-year stroke recurrence (adjusted hazards ratio [HR], 1.31; 95% CI, 1.05-1.64; p = .02) in comparison to those without Diabetes mellitus. Using a competing risk regression model, a diabetes duration ≥8 years was a significant risk factor for stroke recurrence (HR, 1.31; 95% CI, 1.12-1.53). In contrast, there was no significant association between diabetes duration 4, 4 to 8 years and clinical outcomes.Long-term diabetes duration (≥8 years), but not short-term diabetes duration, was associated with an increased risk of 1-year stroke recurrence in patients with ischemic stroke or TIA.

Background: The aim of this study was to investigate the relationship between serum cystatin C levels and the presence and severity of cerebral small vessel disease (CSVD). Methods: Community-dwelling residents in the Lishui city in China from the cross-sectional survey of the PRECISE (Poly-Vascular Evaluation for Cognitive Impairment and Vascular Events) cohort study were included in present study from 2017 to 2019. Total CSVD burden and modified total CSVD burden score, as well as the markers of CSVD on magnetic resonance imaging, including white matter hyperintensity, lacunes, cerebral microbleeds, and perivascular spaces, were assessed at baseline survey. Participants were divided into 4 groups according to the quartiles of cystatin C. The association of serum cystatin C with total CSVD burden and imaging markers was analyzed using ordinal or binary logistic regression models. Furthermore, 2-sample Mendelian randomization analysis was performed to investigate the genetically predicted effect of cystatin C on CSVD. Results: A total of 3061 participants were included in this study. The mean age of the participants was 61.2±6.7 years, and 1637 (53.5%) were women. Higher level of cystatin C was associated with an increased total CSVD burden and modified total CSVD burden (Q4 versus Q1: common odds ratio [OR], 1.30 [95% CI, 1.03–1.64] and 1.32 [95% CI, 1.01–1.73]) after adjustment for covariates. Further, compared with the first quartile of cystatin C, subjects in the last quartile had higher risk of lacunes (OR, 1.99 [95% CI, 1.05–3.76]), modified white matter hyperintensity burden (common OR, 1.42 [95% CI, 1.07–1.90]), and moderate-to-severe perivascular spaces (OR, 2.15 [95% CI, 1.29–3.59]) but not cerebral microbleeds. The Mendelian randomization analysis showed that a genetically predicted higher cystatin C level was associated with increased risk of lacunar stroke (OR, 1.16 [95% CI, 1.06–1.27]). Conclusions: In this community-based study, we found a possible association between cystatin C and CSVD, especially for lacunes, that was independent of estimated glomerular filtration rate.

Associations of air pollution with anxiety and depression were found in previous studies. However, whether air pollution exposure during pregnancy contributes to prenatal anxiety and depression or not is under-investigated. In this study, we aimed to analyze associations between fine particulate matter (PMThis study was based on the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). We used a gap-filling random forest model to estimate PMTotally 3731 pregnant women were included, with the age of 28.85 ± 3.97 years old. Anxiety and depression rates were 10.8 % and 11.5 % respectively, according to the cut-off value of SAS and CES-D. Generalized linear regression results showed that the increase of PMThe increased risk of anxiety or depression was related to PM

Gamma-glutamyl transferase (GGT) is considered a marker of oxidative stress in vivo. In this study, we aimed to examine the association of serum GGT levels with 3-month and 1-year stroke recurrence in patients with acute ischemic stroke or transient ischemic attack (TIA).We conducted a large and multicenter cohort study. Participants with ischemic stroke or TIA who had a baseline GGT measurement were enrolled in the China National Stroke Registry-3 study from August 2015 to March 2018. They were divided into four groups according to sex-specific quartiles of GGT levels. The effect of GGT on stroke recurrence and other vascular events was examined during the 1-year follow-up period. Multivariate Cox regression models were performed to evaluate the association. Discrimination tests were used to examine the degree to which incorporating GGT into the conventional model predicted stroke adverse outcomes.A total of 12,504 patients were enrolled. At both the 3-month and 1-year follow-ups, patients in the highest quartile group of GGT levels exhibited a higher risk of stroke recurrence [HR 1.32 (95% CI 1.07-1.63), HR 1.34 (95% CI 1.13-1.60)], ischemic stroke [HR 1.37 (95% CI 1.10-1.71), HR 1.37 (95% CI 1.14-1.64)], and combined vascular events [HR 1.34 (95% CI 1.09-1.65), HR 1.34 (95% CI 1.13-1.59)] than those in the lowest quartile group. Moreover, the Kaplan-Meier curves revealed that the incidence rates of stroke adverse outcomes were quite different in the four groups. The highest quartile group showed the highest cumulative incidence, while the lowest quartile group showed the lowest cumulative incidence. After applying discrimination tests, adding GGT into the conventional model resulted in slight improvements in predicting stroke adverse outcomes (NRI: 10%-14%).This study demonstrated that elevated GGT levels were positively associated with an increased risk of stroke adverse outcomes, namely, recurrence, ischemic stroke, and combined vascular events.

We aim to evaluate the risk of stroke recurrence among non-diabetes mellitus (non-DM), previously diagnosed diabetes mellitus (PDDM), newly diagnosed diabetes mellitus-related hyperglycemia (NDDM-RH) and stress hyperglycemia after minor stroke or TIA. Totally, 3026 patients with baseline fasting glucose and glycated albumin from the CHANCE trial (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) were included. Patients were classified as non-DM, PDDM, NDDM-RH and stress hyperglycemia according to the status of glucose metabolism. The primary outcome was stroke recurrence during 90-day follow up. Cox regression was performed to estimate the relationship between the status of glucose metabolism and risk of 90-day stroke recurrence. Compared with PDDM, NDDM-RH had a similar risk of 90-day stroke recurrence (hazard ratios [HR]1.39, 95% confidence intervals [CI] 0.94-2.04), while stress hyperglycemia had approximately a 5.3-fold increased risk of 90-day stroke recurrence after adjusted for confounding covariates (HR 5.32, 95% CI 3.43-8.26). Parallel results were found for 90-day recurrent ischemic stroke and composite events. Compared with PDDM in minor stroke or TIA, a parallel risk of 90-day stroke recurrence were observed for NDDM-RH, while stress hyperglycemia might relate to higher risk of 90-day stroke recurrence.

High on-treatment platelet reactivity (HOPR) is associated with stroke recurrence. It is important to find a reliable method to assess HOPR. We aimed to compare the correlations between VerifyNow™ system, thromboelastography (TEG), and Aggrestar platelet function analyzer (PL-12) on platelet activity in patients with minor ischemic stroke or transient ischemic attack (TIA) after dual antiplatelet therapy for 7 days. About 276 patients were included. Spearman’s correlation coefficient and the kappa coefficient were adopted to evaluate associations among the three test methods. An obvious correlation between VerifyNow and TEG on HOPR-ADP (r=0.64, p

Background and Purpose: We assessed prospectively whether nonalcoholic fatty liver disease (NAFLD) and its severity predict future ischemic stroke (IS) events in a community-based cohort. Methods: From the Kailuan study, participants free of history of stroke, cancer, or myocardial infarction were enrolled after excluding alcohol abuse and other liver diseases. NAFLD was evaluated through ultrasonography. Participants with NAFLD were further stratified into mild, moderate, and severe groups. The outcome was the first occurrence of IS. The secondary outcomes included myocardial infarction and combined vascular events. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of incident IS according to presence and severity of NAFLD, adjusting for age, sex, physical activity, body mass index, smoker, history of hypertension, diabetes, hypercholesterolemia, lipid-lowering medication, HDL (high-density lipoprotein), triglyceride, hsCRP (high-sensitivity C-reactive protein), and fasting blood glucose. Results: During a median of 10.34 years of follow-up, we documented 3490 incident stroke cases among 79 905 participants. NAFLD was found in 24 874 (31.18%) participants. Relative to participants without NAFLD at the baseline, those with NAFLD had a 16% higher risk (95% CI, 1.07–1.26) of developing ischemic stroke, after adjusted for confounding variables. The hazard ratios for patients with mild, moderate, and severe NAFLD were 1.15 (95% CI, 1.05–1.25), 1.19 (95% CI, 1.06–1.34), and 1.21 (95% CI, 1.08–1.50), respectively. Conclusions: The severity of NAFLD is associated with a higher risk of future ischemic stroke events.

Studies on antiplatelet effect of ticagrelor/aspirin and clopidogrel/aspirin in patients with acute minor stroke and transient ischemic attack (TIA) stratified by CYP2C19 metabolizer status is limited. We gained data from the Platelet Reactivity In Non-disabling Cerebrovascular Events study. Platelet reactivity was tested at baseline, 2 hours, 24 hours, 7 days and 90 days after initial dose, including high on-treatment platelet reactivity (HOPR), which was defined as P2Y12 reaction unit >208, and percentage inhibition of platelet aggregation (IPA). A total of 365 patients were included. There were 199 (54.5%) individuals classified as carriers of CYP2C19 loss-of-function alleles. For carriers and non-carriers, the proportions of HOPR were significantly lower in those with ticagrelor/aspirin compared with those with clopidogrel/aspirin at 2 hours, 24 hours, 7 days, respectively (all p

Klebsiella pneumoniae (K. pneumoniae) is one of the main environmental pathogens causing bovine mastitis. The incidence of bovine mastitis caused by K. pneumoniae is increasing worldwide. Selenium is an essential trace element that has multiple physiological functions, such as antioxidant and anti-inflammatory activities. Therefore, this study aimed to verify whether selenomethionine (SeMet) could contribute to alleviating the inflammatory injury and oxidative damage induced by K. pneumoniae. Bovine mammary epithelial cells were cultured in vitro and pretreated with 4 μM SeMet before being infected with K. pneumoniae. Western blot analysis was used to detect the expression of the related proteins in the NF-κB and Nrf2 signaling pathways. The gene expression levels of IL-1β, IL-6, IL-8, TNF-α, Nrf2, Keap1, NQO-1 and HO-1 were detected using RT-qPCR. The levels of MDA, GSH-PX, SOD, CAT and T-AOC were detected by commercial assay kits. Flow cytometry was used to determine the level of intracellular ROS, and immunofluorescence was used to detect the nuclear localization of Nrf2 protein. Briefly, SeMet downregulated the phosphorylation levels of IκBα and p65 proteins and the gene expression levels of IL-1β, IL-6, IL-8 and TNF-α were also decreased. Moreover, the protein and gene expression levels of Nrf2, NQO-1 and HO-1 were upregulated, and the nuclear expression of Nrf2 protein was also promoted, which enhanced the activity of antioxidant enzymes. In conclusion, SeMet protected BMECs from inflammatory injury and oxidative stress induced by K. pneumoniae by inhibiting the NF-κB and activating the Nrf2 signaling pathway.

Background Many patients after stroke are found to have elevated serum creatine kinase (CK). This study aimed to investigate the associations between serum CK levels and clinical outcomes in patients with acute ischemic stroke or transient ischemic attack. Methods and Results The study included 8910 patients with acute ischemic stroke or transient ischemic attack from the CNSR‐III (Third China National Stroke Registry). Baseline serum CK levels after admission were measured. The associations between CK and clinical outcomes (stroke recurrence, death, and disability, defined as modified Rankin scale score 3–6 or 2–6) were analyzed. Patients with elevated CK levels had higher risks of recurrent stroke (hazard ratio [HR], 1.53; 95% CI, 1.21–1.93), death (HR, 1.68; 95% CI, 1.10–2.58), and disability (modified Rankin scale score, 3–6; odds ratio, 1.57; 95% CI, 1.29–1.90) at 3 months after adjusting confounding factors. Similar results were found at 1 year. The effects of CK on death and disability were more significant in male patients than female patients ( P value for interaction Conclusions Elevated serum CK after ischemic stroke or transient ischemic attack is associated with higher risks of recurrent stroke, death, and disability at 3 months and 1 year. Serum CK may act as a useful predictor for recurrent stroke and poor functional outcomes in patients with acute ischemic stroke or transient ischemic attack. Sex modifies the relationship between elevated CK and disability or death.

Previously, we identified differentially expressed proteins, including ADFP, between lung adenocarcinoma (LAC) tissue and paired normal bronchioloalveolar epithelium. In this study, we investigated the role of ADFP in LAC. ADFP levels in the serum of patients with lung cancer and benign diseases were measured by enzyme‐linked immunosorbent assays (ELISA). shRNA was used to knock‐down or overexpress ADFP in A549 and NCI‐H1299 cells. The biological function of ADFP and its underlying mechanisms was evaluated in vivo and in vitro. ADFP was highly expressed in the serum of lung cancer patients, especially those with LAC. ADFP promoted cell proliferation and up‐regulated the p‐Akt/Akt ratio in A549 and NCI‐H1299 cells in vitro. Furthermore, in nude mice, ADFP promoted tumour formation with high levels of p‐Akt/Akt, Ki67 and proliferating cell nuclear antigen (PCNA). Similar to the effect of ADFP knock‐down, MK‐2206 (a phosphorylation inhibitor of Akt) reduced A549 and NCI‐H1299 cell proliferation. In ADFP‐overexpressing A549 and NCI‐H1299 cells, proliferation was suppressed by MK‐2206 and returned to the control level. ADFP did not regulate invasion, migration or adhesion in LAC cells. Together, these results suggest that ADFP promotes LAC cell proliferation in vitro and in vivo by increasing Akt phosphorylation level.

In this study, we tested the effect of ticagrelor versus clopidogrel on platelet reactivity in patients with minor stroke or transient ischemic attack (TIA). A pre-specified subgroup analysis of a randomized controlled trial was conducted. Platelet reactivity was assessed by thrombelastography (TEG) platelet mapping. Patients were divided into carriers and non-carriers according to the carrier status of CYP2C19 loss-of-function (LOF) alleles. The primary outcome was the proportion of patients with high on-treatment platelet reactivity (HOPR) (defined as maximum amplitude induced by adenosine diphosphate > 47mm) at 90±7 days. Clinical outcomes within 90±7 days were followed up. Among 339 patients, 170 were randomized to ticagrelor/aspirin and 169 to clopidogrel/aspirin. Compared with clopidogrel/aspirin, the proportion of HOPR at 90±7 days in ticagrelor/aspirin was significantly lower (12.2% versus 30.0%, P < 0.001). Ticagrelor/aspirin had a lower proportion of HOPR among carriers (11.0% versus 35.6%, P < 0.001), but not among non-carriers (13.5% versus 22.4%, P = 0.17). Ticagrelor was superior to clopidogrel in inhibiting platelet reactivity measured by TEG platelet mapping among patients with acute minor stroke or TIA, particularly in carriers of the CYP2C19 LOF alleles. Large randomised controlled trials are needed to confirm our findings.

Background and purposePrevious studies have reported conflicting results as to whether women have poorer functional outcome than men after thrombolytic therapy. This study aims to investigate the relationship between sex differences and the prognosis of intravenous thrombolysis in Chinese patients with acute ischaemic stroke.MethodsThe patients enrolled in this study were from the Chinese Acute Ischemic Stroke Thrombolysis Monitoring and Registration study. The primary outcome was poor functional outcome, defined as a 3-month modified Rankin score of 3–6. The safe outcome was symptomatic intracranial haemorrhage (SICH) and mortality within 7 days and 90 days. Multiple Cox regression model was used to correct the potential covariates to evaluate the association between sex disparities and prognosis. Furthermore, the interaction of preonset Rankin scores, baseline National Institute of Health Stroke Scale (NIHSS) scores and Trial of Org 10172 in Acute Stroke Treatment (TOAST) types was statistically analysed.ResultsA total of 1440 patients were recruited, including 541 women and 899 men. The baseline information indicated that women were older at the time of onset (66.2±11.2 years vs 61.0±11.3 years, pConclusionsFor Chinese patients with ischaemic stroke, although women are older and more severe at the time of onset, the prognosis after intravenous thrombolysis is not significantly different from men.

IntroductionDNA methylation is currently found to be associated with the progression of cervical intraepithelial neoplasia and the development of cervical cancer. The aim of this study was to analyze the role of real time quantitative methylation detection of the PAX1 gene in cervical cancer screening.MethodsAll eligible patients who underwent multiple detections for cervical cancer were assigned to the normal cervical group (n=21), cervical intraepithelial neoplasia I group (n=7), cervical intraepithelial neoplasia II+III group (n=12), or invasive cervical cancer group (n=14) based on pathological gradings. The methylation level of the PAX1 gene was detected using the real time quantitative methylation specific polymerase chain reaction assay and assessed by △Cp value. The diagnostic performance of PAX1 methylation detection was compared with folic acid receptor mediated diagnosis, the Thinprep cytology test, and human papilloma virus (HPV) testing.ResultsThe △Cp value in the invasive cervical cancer group was (6.15±4.07), significantly lower than that in the other groups (F=26.45, pConclusionThrough quantitative methylation specific polymerase chain reaction assay characterized by rapid screening and simple operation, the methylation detection of the PAX1 gene exhibited a higher diagnostic performance and may be a promising method for cervical cancer screening.

Background: A single index of body mass index (BMI) may not fully address its impact on anti-platelet therapy. We aimed to elucidate the combined impact of BMI and dysglycemia expressed by glycated albumin (GA) on efficacy of clopidogrel-aspirin therapy among minor stroke (MS) or transient ischemic attack (TIA) patients. Results: Patients with overweight/obesity and low GA levels still benefited from clopidogrel-aspirin therapy for stroke recurrence (Hazard ratio [HR]: 0.48, 95 % confidence interval [CI]: 0.28–0.82), so did those with high GA levels but low/normal weight (HR: 0.67, 95 % CI: 0.45–0.99). However, patients with both overweight/obesity and high GA levels did not benefit from clopidogrel-aspirin therapy (HR: 0.89, 95 % CI: 0.59–1.33). Conclusions: Compared with aspirin alone, efficacy of clopidogrel-aspirin therapy for stroke still exists in overweight/obesity patients with normal glycemic control. Methods: In Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events trial, 3044 patients with available baseline GA were recruited. Low/normal weight and overweight/obesity were defined as BMI < 25 kg/m2 and ≥ 25 kg/m2, respectively. Elevated and low GA levels were defined as GA levels > 15.5 % and ≤ 15.5 %, respectively. The primary outcome was stroke recurrence during the 90-day follow-up.

Background This study aims to demonstrate the impact of the cumulative burden of low density lipoprotein-cholesterol (cumLDL-c) and high sensitivity C-reactive protein (cumhs-CRP) on cardiovascular risk. Results During the 4.62 (±0.70) years of follow-up, 2,148 (5.92%) participants had MACE. Both of cumLDL-c and cumhs-CRP were independent risk factors for MACE. In participants without cumLDL-c during 2006-2013, the participants with cumhs-CRP had higher MACE risk during the subsequent 5 years, than those without cumhs-CRP (hazard ratio [HR]: 1.24, 95% confidence interval [CI]:1.04-1.47). In addition, cumhs-CRP correlated with MACE in a cumhs-CRP level-dependent pattern. Conclusion This study validated the effects of residual inflammation risk in patients with low LDL-c Level in a general population, using long-term burdens of hs-CRP or LDL-c other than a single time-point level. Method The Kailuan study is a prospective, population-based study began in 2006. These total 36,421 participants completed 4 measurements of hs-CRP and LDL-c biennially from 2006-2013. Cumhs-CRP or cumLDL-c levels were calculated as the number of interval years multiplied by the Δhs-CRP (more than 2.0 mg/L) or ΔLDL-c (more than 2.6 mmol/L). Outcomes measured during follow-up (2012-2017) were defined as major adverse cardiac events (MACE), including ischemic stroke, myocardial infarction, and all-cause mortality.

BackgroundThe effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear.MethodsData of 1045 patients with minor stroke or transient ischaemic attack (TIA) were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale (mRS) scores using ordinal logistic regression models.ResultsAmong the 1045 patients, CSVD was present in 830 cases (79.4%) and ICAS in 460 (44.0%). Patients with >1 ICAS segment showed the highest risk of new strokes (HR 2.03, 95% CI 1.15 to 3.56, p=0.01). No association between CSVD and the occurrence of new strokes was found. The presence of severe CSVD (common OR (cOR) 2.01, 95% CI 1.40 to 2.89, p1 ICAS segment (cOR 2.15, 95% CI 1.57 to 2.93, pInterpretationCSVD is associated with more disability and bleeding events, and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months. CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes.Trial registration numberNCT00979589

Low-density lipoprotein (LDL) and oxidized low-density lipoprotein (oxLDL) levels are thought to be related to recurrent stroke. However, the joint association of circulating LDL and oxLDL levels with the outcomes of acute minor ischemic stroke and transient ischemic attack (TIA) remains unclear. The goal of the study was to evaluate whether LDL and oxLDL have a combined effect on outcomes of acute minor stroke and TIA.In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, a subgroup of 3019 patients with baseline oxLDL and LDL levels were analyzed. Patients were divided into four groups according to different combinations of LDL (LDL 3.37 mmol/L, LDL ≥ 3.37 mmol/L) and oxLDL levels (oxLDL13.96 μg/dL, oxLDL ≥ 13.96 μg/dL). The primary outcome was any stroke within 90 days. The secondary outcomes included any stroke within 1 year and ischemic stroke and combined vascular events within 90 days and 1 year. The poor functional outcome included modified Rankin Scale (mRS) 3-6 at 90-day and 12-month follow-up. The association of LDL and oxLDL with the prognosis of patients was examined using multivariable Cox regression models.Among 3019 patients included in this study, the medians (interquartile range) of oxLDL and LDL were 13.96 (6.65-28.81) μg/dL and 3.1 (2.5-3.8) mmol/L, respectively. The cumulative occurrence of recurrent stroke, ischemic stroke, and combined vascular events was 9.74%, 9.54%, and 9.80% within 90 days of follow-up. Compared with those with low LDL and oxLDL levels (LDL 3.37 mmol/L with oxLDL13.96 μg/dL), patients with high levels of LDL and oxLDL (LDL ≥3.37 mmol/L, oxLDL ≥13.96 μg/dL) had significantly increased risk of recurrent stroke at 90 days (HR,1.57; 95% CI, 1.10-2.24) and 1 year (HR,1.49; 95% CI, 1.10-2.04). Patients in groups with LDL ≥3.37 mmol/L, oxLDL13.96 μg/dL (HR,1.35; 95% CI, 0.94-1.93) or LDL 3.37 mmol/L with oxLDL ≥13.96 μg/dL (HR,1.11; 95% CI, 0.77-1.59) showed no statistical difference for stroke recurrence. Similar results were found for functional outcomes.The presence of higher combined serum oxLDL and LDL levels was associated with increased risk of recurrent stroke and poor functional outcomes in minor stroke or high-risk TIA patients.

Staphylococcus aureus is a pathogen that is the causative agent of several human and veterinary infections and plays a critical role in the clinical and subclinical mastitis of cattle. Autophagy is a conserved pathogen defence mechanism in eukaryotes. Studies have reported that S aureus can subvert autophagy and survive in cells. Staphylococcus aureus survival in cells is an important cause of chronic persistent mastitis infection. However, it is unclear whether S aureus can escape autophagy in innate immune cells. In this study, initiation of autophagy due to the presence of S aureus was detected in bovine macrophages. We observed autophagic vacuoles increased after S aureus infection of bovine macrophages by transmission electron microscopy (TEM). It was also found that S aureus‐infected bovine macrophages increased the expression of LC3 at different times(0, 0.5, 1, 1.5, 2, 2.5, 3 and 4 hours). Data also showed the accumulation of p62 induced by S aureus infection. Application of autophagy regulatory agents showed that the degradation of p62 was blocked in S aureus induced bovine macrophages. In addition, we also found that the accumulation of autophagosomes promotes S aureus to survive in macrophage cells. In conclusion, this study indicates that autophagy occurs in S aureus‐infected bovine macrophages but is blocked at a later stage of autophagy. The accumulation of autophagosomes facilitates the survival of S aureus in bovine macrophages. These findings provide new insights into the interaction of S aureus with autophagy in bovine macrophages.

Background: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study. Methods: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups. Results: One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P Conclusions: Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients.

Background This study investigated the relationships of neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) with cerebral small vessel disease (CSVD). Methods A total of 3052 community-dwelling residents from the Poly-vasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were involved in this cross-sectional study. CSVD burden and imaging markers, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS), were assessed according to total CSVD burden score. The associations of NC, NLR and SII with CSVD and imaging markers were evaluated using logistic regression models. Furthermore, two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of NC on CSVD. The prognostic performances of NC, NLR and SII for the presence of CSVD were assessed. Results At baseline, the mean age was 61.2 ± 6.7 years, and 53.5% of the participants were female. Higher NC was suggestively associated with increased total CSVD burden and modified total CSVD burden (Q4 vs. Q1: common odds ratio (cOR) 1.33, 95% CI 1.05–1.70; cOR 1.28, 95% CI 1.02–1.60) and marginally correlated with the presence of CSVD (OR 1.29, 95% CI 1.00–1.66). Furthermore, elevated NC was linked to a higher risk of lacune (OR 2.13, 95% CI 1.25–3.62) and moderate-to-severe BG-EPVS (OR 1.67, 95% CI 1.14–2.44). A greater NLR was related to moderate-to-severe BG-EPVS (OR 1.68, 95% CI 1.16–2.45). Individuals with a higher SII had an increased risk of modified WMH burden (OR 1.35, 95% CI 1.08–1.69) and moderate-to-severe BG-EPVS (OR 1.70, 95% CI 1.20–2.41). MR analysis showed that genetically predicted higher NC was associated with an increased risk of lacunar stroke (OR 1.20, 95% CI 1.04–1.39) and small vessel stroke (OR 1.21, 95% CI 1.06–1.38). The addition of NC to the basic model with traditional risk factors improved the predictive ability for the presence of CSVD, as validated by the net reclassification index and integrated discrimination index (all p Conclusions This community-based population study found a suggestive association between NC and CSVD, especially for BG-EPVS and lacune, and provided evidence supporting the prognostic significance of NC.

Significance Neuronal innervation in the adipose tissues plays a crucial role in regulating adipose thermogenic capacity and metabolic homeostasis. The tissue-wide nerves display a large extent of structural plasticity under physiological and pathological conditions that alter the neuronal control of metabolic states. We find here that neuronal plasticity is regulated by immune cells, which constitutes an appealing way to reshape neural-controlled energy balance by targeting immune components., Sympathetic innervation regulates energy balance, and the nerve density in the adipose tissues changes under various metabolic states, resulting in altered neuronal control and conferring resilience to metabolic challenges. However, the impact of the immune milieu on neuronal innervation is not known. Here, we examined the regulatory role on nerve plasticity by eosinophils and found they increased cell abundance in response to cold and produced nerve growth factor (NGF) in the white adipose tissues (WAT). Deletion of Ngf from eosinophils or depletion of eosinophils impairs cold-induced axonal outgrowth and beiging process. The spatial proximity between sympathetic nerves, IL-33–expressing stromal cells, and eosinophils was visualized in both human and mouse adipose tissues. At the cellular level, the sympathetic adrenergic signal induced calcium flux in the stromal cells and subsequent release of IL-33, which drove the up-regulation of IL-5 from group 2 innate lymphoid cells (ILC2s), leading to eosinophil accretion. We propose a feed-forward loop between sympathetic activity and type 2 immunity that coordinately enhances sympathetic innervation and promotes energy expenditure.

Post-stroke inflammation biomarker high-sensitivity C-reactive protein (hsCRP) increases cerebral infarct size and results in functional disability directly, it also contributes to the formation and maturation of atherosclerotic plaques, which increase the risk of stroke recurrence and results in functional disability indirectly. However, no study has quantified how much functional disability was mediated by stroke recurrence.Patients with acute ischaemic stroke within 7 days and admitted to 169 hospitals in the Third China National Stroke Registry were analyzed. Blood samples were collected within 24 h of admission. Stroke recurrence and functional disability (defined as a modified Rankin scale score ≥ 2) were assessed via face-to-face interviews at three months. Mediation analysis under the counterfactual framework was performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between hsCRP and functional outcome. Sensitivity analyses were performed across different subgroups and on different scales of hsCRP measurement.Of the 7603 analyzed patients (mean [SD] age, 62.3 [11.3] years; 2392 [31.5%] women), the median (interquartile range [IQR]) of NIHSS score was 3.0 (1.0-6.0). The median (IQR) level of hsCRP was 1.73 (0.81-4.38) mg/L. A total of 496 (6.5%) cases of stroke recurrence and 1884 (24.8%) cases of functional disability were observed at the 90-day follow-up. Each SD increase in the concentration of hsCRP was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.11; 95% CI, 1.04-1.18) and disability (aOR, 1.14; 95% CI, 1.08-1.20) within 90 days. Of 1884 functionally disabled patients, only 16.0 % (n = 302) of patients experienced stroke recurrence before functional disability. Stroke recurrence during follow-up explained 16.52% (95% CI, 5.79%-27.25%) of the relationship between hsCRP and functional disability. Sensitivity analyses in different subgroups and on different scales of hsCRP measurement showed comparable results.Stroke recurrence mediates less than 20% of the association between hsCRP and functional disability at 90 days among patients with acute ischaemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes.Beijing Natural Science Foundation, the National Key RD Program of China, the National Natural Science Foundation of China, and the Beijing Municipal ScienceTechnology Commission.

Associations between individual exposure to ozone (OWe aimed to explore the associations of gestational OA total of 7834 pregnant women were included. Individual ONearly 13.29 % of participants developed GDM. After controlling for covariates, we observed increased GDM risks per IQR increment of OIn summary, we found that gestational O

Background The association of lipoprotein(a) [Lp(a)] and stroke functional outcomes was conflicting. The aim of the study was to clarify whether high Lp(a) is associated with unfavorable functional outcomes in patients with ischemic stroke. Methods A total of 9709 individuals from the third China National Stroke Registry cohort were recruited. Plasma level of Lp(a) at admission was measured with enzyme-linked immunosorbent assay. The cut-off was set at the median for Lp(a). Functional outcome was assessed using the modified Rankin scale (mRS) at 3 months and 1 year after ischemic stroke. The association between Lp(a) and functional outcomes was evaluated using a logistic regression model. Results The median age was 63.0 years, and 31.1% participants were women. Patients in higher Lp(a) group had higher incidences of unfavorable functional outcomes at 3 months. In logistic regression model, elevated Lp(a) levels were associated with unfavorable functional outcomes at 3 months (Q4 vs. Q1: odds ratio 1.33, 95% confidence interval 1.11–1.61). Subgroup analysis showed that in the lower Lp-PLA2 group, Lp(a) level was not associated with functional outcomes, but in the higher Lp-PLA2 group, Lp(a) level was significantly associated with functional outcomes. After grouped by different levels of Lp(a) and Lp-PLA2, the Lp(a) high/ Lp-PLA2 high group showed the highest incidence of unfavorable functional outcomes at 3 months and 1 year. Conclusions Elevated Lp(a) level is associated with unfavorable functional outcomes in patients with ischemic stroke. The increment in both Lp(a) and Lp-PLA2 are associated with unfavorable functional outcomes at 3 months and 1 year after ischemic stroke.

Rationale It remains unknown whether long-term ozone exposure can impair lung function. Objectives To investigate the associations between long-term ozone exposure and adult lung function in China. Methods Lung function results and diagnosis of small airways dysfunction (SAD) were collected from a cross-sectional study, China Pulmonary Health Study (N=50,991). We used multivariate linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trend. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and main results We observed each 1-standard deviation (SD, 4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 mL/s [95% confidence interval (CI): 8.8, 19.6] decrease in forced expiratory flow at 75th percentile of vital capacity and a 29.5 mL/s (95% CI: 19.6, 39.5) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI: 1.06, 1.11) for a 1-SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with a decreased ratio of expiratory volume in 1 second to forced vital capacity (FEV1/FVC) but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusion We found independent associations of long-term ozone exposure with impaired small airways function and higher SAD risks, while the associations with airflow obstruction were weak. COPD patients appear to be more vulnerable.

Exposure to fine particulate matter (PM

Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke inWe conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carriedA total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively.Among Chinese patients with minor ischemic stroke or TIA who were carriers of

Background and Purpose: The age, body mass index, chronic kidney disease, diabetes, and genotyping (ABCD-GENE) score is a validated risk score integrating CYP2C19 genotypes with clinical risk factors influencing clopidogrel response that would allow the more precise identification of subjects at risk for high platelet reactivity and adverse clinical outcomes. Our objective was to further verify application of the ABCD-GENE score and investigate appropriate cutoff value in patients with minor stroke or transient ischemic attack. Methods: In this post-analysis of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), the ABCD-GENE score was calculated for all patients enrolled in this study. By using the proposed cutoff of 10, patients were stratified as being at high risk for high platelet reactivity or not. We further categorized the ABCD-GENE score to 0 to 5, 6 to 24, and >24 to investigate the cutoff value of this scale in clinical application. Stroke recurrence at 3 months was considered as the primary outcome. Results: Among a total of 2923 patients with minor stroke/transient ischemic attack, there were 2273 (77.76%) with ABCD-GENE score 24, hazard ratios of the clopidogrel-aspirin therapy for stroke recurrence were 0.57 (95% CI, 0.38–0.85), 0.78 (0.58–1.06), and 1.20 (0.44–3.28) ( P value for trend=0.0052). Conclusions: Among Chinese minor stroke/transient ischemic attack population, the efficacy of clopidogrel-aspirin therapy was decreased in patients with higher ABCD-GENE score. Our study suggests that CYP2C19 genotypes and clinical risk factors can be integrated by ABCD-GENE score to estimate the efficacy of clopidogrel-aspirin therapy.

China faces the greatest challenge from stroke in the world. According to results from the Global Burden of Disease Study 2019, there were 3.94 million new stroke cases, 28.76 million prevalent cases and 2.19 million deaths due to stroke in China in 2019. Furthermore, stroke is also the leading cause of disability-adjusted life-year (DALY) in China, the number of DALYs reached 45.9 million in 2019. Several recent large-scale epidemiological surveys have updated the data on pre-existing conditions contributed to stroke. The age-adjusted prevalence of overweight among Chinese adults aged 18–69 years was 34.4%, and the prevalence of obesity was 16.8% in 2018. 50.9% of Chinese adults ≥18 years of age without history of hypertension had prehypertension in 2018. The weighted prevalence of hypertension in adults was 27.5% in 2018. The weighted prevalence of total diabetes and pre-diabetes diagnosed by the American Diabetes Association criteria were 12.8% and 35.2%, respectively, among Chinese adults ≥18 years of age in 2017. The weighted atrial fibrillation prevalence was 1.8% among Chinese adults ≥45 years of age and equates to being present in an estimated 7.9 million people in China. Data from 1672 tertiary public hospitals in the Hospital Quality Monitoring System (HQMS) showed that 3 411 168 stroke cases were admitted during 2019. Of those, 2 818 875 (82.6%) were ischaemic strokes (ISs), 485 474 (14.2%) were intracerebral haemorrhages (ICHs), 106 819 (3.1%) were subarachnoid haemorrhages (SAHs). The average age was 66 years old, and 59.6% were male. A total of 1379 (

Background and Purpose: To investigate the prevalence of malnutrition risk in patients with acute ischemic stroke (AIS) at admission, the association between malnutrition risk and long-term outcomes, and whether the predictive ability would be improved after adding to previous prognostic models for poor outcomes. Methods: Based on the Third China National Stroke Registry data from August 2015 to March 2018, we evaluated malnutrition risk using objective scores, including the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index. The primary outcome was death or major disability (modified Rankin Scale score ≥3) at 1 year after stroke onset. We calculated the crude prevalence of malnutrition risk and investigated the association between malnutrition risk and clinical outcomes. Prognostic performance of 3 objective malnutrition scores for poor outcomes was assessed. Results: Moderate to severe malnutrition risk was identified in 5.89%, 5.30%, and 1.95% of the Third China National Stroke Registry AIS patients according to the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index, respectively. At 1-year follow-up, 1143 participants (13.5%) experienced death or major disability. After adjustment for traditional risk factors, moderate to severe malnutrition risk was associated with high risk of composite events (odds ratio, 2.25 [95% CI, 1.75–2.90], for controlling nutritional status score; odds ratio, 2.10 [95% CI, 1.63–2.69], for geriatric nutritional risk index; odds ratio, 3.36 [95% CI, 2.33–4.84], for prognostic nutritional index; all P P Conclusions: The prevalence of moderate or severe malnutrition risk in Chinese patients with AIS ranged from 1.95% to 5.89%. Malnutrition risk in patients with AIS was associated with increased risk of long-term death and major disability. Our study provides evidence supporting the prognostic significance of objective malnutrition scores after AIS.

Background: Fine particulate matter (PM2.5) exposure has been reported to adversely affect birth outcomes, but the evidence is limited, particularly in low- and middle-income countries (LMICs). We assessed the associations between maternal PM2.5 exposure and low birth weight (LBW) and preterm birth (PTB) in Africa. Methods: We used standard Demographic and Health Surveys (DHS) data (2005–2015) from 15 countries in Africa to conduct a cross-sectional study. The study population was composed of 131,594 births with detailed information on maternal and household variables. LBW was defined as a birth weight of

Background Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. Methods Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). Results Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs Conclusions Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Staphylococcus aureus (S. aureus) is known to induce chronic and persistent bovine mammary infection, which affects milk quality and leads to premature culling. The ability of S. aureus to invade mammalian cells protects it from clearance by the immune system. Mitophagy is important in cell homeostasis, and can be utilized by pathogens for immune escape. However, mitophagy's role in S. aureus-associated bovine mastitis remains unclear. Here, S. aureus infection induced mitophagy and enhanced mitochondrial translocation of parkin in MAC-T cells. After mitophagy inhibition by Mdivi-1 treatment or PTEN-induced putative kinase 1 (PINK1) silencing in MAC-T cells infected with S. aureus, NOD-like receptor protein 3 (NLRP3) inflammasome activation and p65 and IκBα phosphorylation were increased. Meanwhile, PINK1 overexpression had the opposite effects. In addition, NLRP3 inflammasome overactivation and enhanced p65 and IκBα phosphorylation caused by PINK1 silencing were reversed by MitoTEMPO. Furthermore, PINK1/parkin-mediated mitophagy promoted S. aureus survival and contributed to persistent S. aureus infection. These findings provide new insights into S. aureus invasion in bovine mastitis.

Cervical cancer (CC) is a common gynaecological malignant tumour with a high mortality rate. Circular RNAs (circRNAs) play a critical role in tumour occurrence and development. This study aimed to investigate the function and molecular basis of hsa_circ_0009189 (circSAMD11) in CC development. RNA levels were determined by qRT-PCR, and protein expression was measured by western blot. Cell proliferation, migration, invasion and apoptosis were detected by Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometry assays. The relationship between miR-503 and circSAMD11/SOX4 was validated via dual-luciferase reporter assay, RIP or RNA pull-down assay. Xenograft assay was conducted to test tumour growth in vivo. CircSAMD11 and SOX4 levels were elevated, while miR-503 level was reduced in CC tissues and cells. Knockdown of circSAMD11 suppressed CC cell proliferation, migration and invasion and accelerated apoptosis. CircSAMD11 was localised in cytoplasm and directly targeted miR-503. Also, circSAMD11 sponged miR-503 to modulate SOX4 expression. Additionally, circSAMD11 regulated CC progression via absorbing miR-503 or modulating SOX4. Besides, depletion of circSAMD11 hindered tumorigenesis in vivo. CircSAMD11 contributed to CC progression by regulating miR-503/SOX4 signalling and activating Wnt/β-catenin pathway, which provides a promising therapeutic target for cervical cancer.

Key Points Question Do prescribers in China follow established guidelines for prescription of oral anticoagulants (OACs) to patients with ischemic stroke and atrial fibrillation, and has adherence to prescribing guidelines changed over time? Findings In this multicenter quality improvement study, among 35 767 eligible patients with ischemic stroke and atrial fibrillation at admission, fewer than 1 in 5 were taking OACs at admission, and of 49 531 eligible patients at discharge, only 41% were prescribed OACs at discharge. Although adherence to OACs has significantly improved over time, it remains suboptimal; the increase was mainly associated with warfarin, not non–vitamin K antagonist OACs. Meaning This study suggests that more specific programs educating physicians and patients are needed to ensure that OACs, especially non–vitamin K OACs, are prescribed to eligible patients., Importance Adherence to oral anticoagulants (OACs) per guideline recommendations is crucial in reducing ischemic stroke and systemic thromboembolism in high-risk patients with ischemic stroke and atrial fibrillation. However, data on OAC use are underreported in China. Objective To assess adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association’s clinical management guideline–recommended prescription of OACs, the temporal improvement in adherence, and the risk factors associated with OAC prescriptions. Design, Setting, and Participants This quality improvement study was conducted at 1430 participating hospitals in the Chinese Stroke Center Alliance (CSCA) among patients with ischemic stroke and atrial fibrillation enrolled in the CSCA between August 1, 2015, and July 31, 2019. Exposure Calendar year. Main Outcomes and Measures Adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association’s clinical management guideline–recommended prescribing of OACs (warfarin and non–vitamin K OACs, including dabigatran, rivaroxaban, apixaban, and edoxaban) at discharge. Results Among 35 767 patients (18 785 women [52.5%]; mean [SD] age, 75.5 [9.2] years) with previous atrial fibrillation at admission, the median CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]–vascular disease, and sex category [female]) score was 4.0 (interquartile range, 3.0-5.0); 6303 (17.6%) were taking OACs prior to hospitalization for stroke, a rate that increased from 14.3% (20 of 140) in the third quarter of 2015 to 21.1% (118 of 560) in the third quarter of 2019 (P, This quality improvement study assesses adherence to guideline-recommended oral anticoagulants, the temporal improvement in adherence, and the risk factors associated with oral anticoagulant prescriptions.