Prognostic Value of Plasma Immunoglobulin G N-Glycome Traits in Pulmonary Arterial Hypertension.

BACKGROUND: B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide is the only blood biomarker in established risk calculators for pulmonary arterial hypertension (PAH). Profiling systemic-originated plasma immunoglobulin G (IgG) N-glycans, which reflect different components of the pathophysiology of PAH including immune dysregulation and inflammation, may improve PAH risk assessment. OBJECTIVES: This study sought to identify plasma IgG N-glycan biomarkers that predict survival in PAH to improve risk assessment. METHODS: This cohort study examined 622 PAH patients from 2 national centers (Beijing [discovery] cohort: n = 273; Shanghai [validation] cohort: n = 349). Plasma IgG N-glycomes were profiled by a robust mass spectrometry-based method. Prognostic IgG N-glycan traits were identified and validated in the 2 cohorts using Cox regression and Kaplan-Meier survival analyses. The added value of IgG N-glycan traits to previously established risk models was assessed using Harrell C-indexes and survival analysis. RESULTS: Plasma IgG fucosylation was found to predict survival independent of age and sex in the discovery cohort (HR: 0.377; 95% CI: 0.168-0.845; P = 0.018) with confirmation in the validation cohort (HR: 0.445; 95% CI: 0.264-0.751; P = 0.005). IgG fucosylation remained a robust predictor of mortality in combined cohorts after full adjustment and in subgroup analyses. Integrating IgG fucosylation into previously established risk models improved their predictive capacity, marked by an overall elevation in Harrell C-indexes. IgG fucosylation was useful in further stratifying the intermediate-risk patients classified by a previously established model. CONCLUSIONS: Plasma IgG fucosylation informs PAH prognosis independent of established factors, offering additional value for predicting PAH outcomes.

Risk factor analysis and nomogram construction of postoperative complications for patients with locally advanced gastric cancer who received neoadjuvant immunotherapy and chemotherapy.

Introduction: The combination of neoadjuvant immunotherapy and chemotherapy (NICT) has become a common treatment regimen for locally advanced gastric cancer (LAGC). However, the safety and efficacy of radical gastrectomy following NICT (NICT-G) remain controversial. This study aimed to analyze the risk factors influencing postoperative complications (POCs) after NICT-G. Additionally, it aimed to construct a nomogram to provide a clinical reference for predicting POCs. Methods: This study included 177 patients who received NICT-G at the Chinese PLA General Hospital First Medical Center from January 2020 to January 2024. Univariable and multivariable logistic regression models were used to evaluate the risk factors influencing POCs, and a nomogram model was constructed. To evaluate the discrimination and accuracy of the nomogram model, the area under the receiver operating characteristic curve (AUC) and the calibration curve were measured. Results: In 177 patients who received NICT-G, the pathological complete response and major pathological response rates were 15.8% and 45.2%, respectively, whereas the rates of the overall and severe treatment-related adverse events were 71.8% and 15.8%, respectively. In addition, 43 (24.3%) patients developed overall POCs (Clavien-Dindo classification ≥ II). Univariable and multivariable logistic analyses showed that age ≥70 years, greater estimated blood loss, platelet/lymphocyte ratio (PLR) ≤196, neutrophil/lymphocyte ratio (NLR) >1.33, non-R0 resection, and body mass index (BMI) < 18.5 kg/m2 were independent risk factors for overall POCs (p < 0.05). The nomogram model developed using the abovementioned variables showed that the AUC (95% confidence interval [CI]) was 0.808 (95% CI): 0.731-0.885 in predicting the POC risk. The calibration curves showed that the prediction curve of the nomogram was a good fit for the actual POCs (Hosmer-Lemeshow test: χ2 = 5.76, P = 0.451). Conclusion: The independent risk factors for overall POCs in the NICT-G were age ≥ 70 years, greater estimated blood loss, PLR ≤ 196, NLR > 1.33, non-R0 resection, and BMI < 18.5 kg/m2. The nomogram model developed based on the abovementioned indicators showed better accuracy in predicting the POC risk.

Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism: A case-control study.

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE. METHODS: In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation. RESULTS: The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P  = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243-5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056-5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792-30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467-8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288-36.484) were independently associated with elevated hs-cTnI. CONCLUSIONS: CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Correlations between the peripheral coronary fat attenuation index based on computed tomography images, high-risk plaque and degree of coronary artery stenosis in patients with coronary atherosclerosis.

BACKGROUND: Coronary artery disease can be quantified by measuring the fat attenuation index (FAI). OBJECTIVE: To explore the correlations between FAI, high-risk plaque and the degree of coronary artery stenosis. METHODS: The clinical data of patients with coronary atherosclerosis who underwent a coronary computed tomography (CT) angiography examination between July 2020 and June 2023 were selected for retrospective analysis. These patients were classified into a high-risk plaque group and non-high-risk plaque group according to the presence of CT high-risk plaque. The diagnostic value of FAI and FAI combined with the degree of stenosis was evaluated for CT high-risk plaque. RESULTS: Differences in age, body mass index, smoking history, FAI and the degree of stenosis between the two groups were statistically significant (all P< 0.05). The results of a binary logistic regression analysis revealed that FAI (odds ratio (OR): 1.131, 95% confidence interval (CI): 1.101-1.173, P< 0.001) and the degree of stenosis (OR: 1.021, 95% CI: 1.012-1.107, P< 0.001) were risk factors for high-risk plaque. CONCLUSION: The FAI can be used to monitor the inflammation level of the coronary artery; the higher the FAI is, the higher the risk of plaque and degree of stenosis.

RNA m6A methylation and regulatory proteins in pulmonary arterial hypertension.

m6A (N6­methyladenosine) is the most common and abundant apparent modification in mRNA of eukaryotes. The modification of m6A is regulated dynamically and reversibly by methyltransferase (writer), demethylase (eraser), and binding protein (reader). It plays a significant role in various processes of mRNA metabolism, including regulation of transcription, maturation, translation, degradation, and stability. Pulmonary arterial hypertension (PAH) is a malignant cardiopulmonary vascular disease characterized by abnormal proliferation of pulmonary artery smooth muscle cells. Despite the existence of several effective and targeted therapies, there is currently no cure for PAH and the prognosis remains poor. Recent studies have highlighted the crucial role of m6A modification in cardiovascular diseases. Investigating the role of RNA m6A methylation in PAH could provide valuable insights for drug development. This review aims to explore the mechanism and function of m6A in the pathogenesis of PAH and discuss the potential targeting of RNA m6A methylation modification as a treatment for PAH.

Microvascular invasion is associated with poor survival in patients with dual-phenotype hepatocellular carcinoma.

OBJECTIVES: Microvascular invasion (MVI) has previously been reported to be related to cancer prognosis; however, its significance in patients with dual-phenotype hepatocellular carcinoma (DPHCC) remains uncharacterized. We studied the role of MVI in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of HCC. METHODS: Patients with DPHCC (n = 84) who had undergone surgical interventions at the 900th Hospital of the Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between MVI and patient survival. RESULTS: Our results indicated that MVI was related to poor survival. According to the univariate analysis, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, the expression of cytokeratin 19 (CK19), and serum levels of both ɑ-fetoprotein (AFP) and cancer antigen-199 showed a strong correlation with overall survival. Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Tumor size; the number of tumor lesions; differentiation; peripheral hepatic fibrosis; liver capsule invasion; and expression of CK19, vascular endothelial growth factor, CK7, and mucin 1 showed a correlation with MVI, per the outcomes of χ2 tests. CONCLUSIONS: Microvascular invasion may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study.

BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1ß and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.

Association Between New-Onset Type 2 Diabetes and Cardiac Conduction Diseases: A Prospective Cohort Study.

BACKGROUND: Cardiac conduction diseases can lead to life-threatening outcomes. However, the evidence on risk factors for conduction disease that is needed to underpin prevention strategies is limited. The present study aimed to determine the association between type 2 diabetes and cardiac conduction diseases. METHODS AND RESULTS: This study included 101 080 participants free of prevalent diabetes and cardiac conduction diseases at baseline from the Kailuan Study. All participants were monitored biennially until December 31, 2020. During follow-up, 14 397 participants were diagnosed as having type 2 diabetes. For each case subject, 1 control subject was randomly selected, matched for age (±1 year) and sex. The final analysis comprised 10 744 case-control pairs. Cox regression models with age as the underlying time scale were used. During a median follow-up of 5.46 years, 571 incident events occurred, including 164 atrioventricular blocks, 414 bundle-branch blocks (BBBs), 274 right BBBs, and 210 left BBBs. After adjustment for potential confounders, participants with type 2 diabetes diagnosed had greater relative risks for most outcomes relative to controls, with hazard ratios of 1.42 (95% CI, 1.18-1.67) for conduction diseases, 1.40 (95% CI, 1.00-1.96) for atrioventricular blocks, 1.43 (95% CI, 1.16-1.75) for BBBs, and 1.69 (95% CI, 1.15-2.49) for left BBBs. In contrast, no association between diabetes and right BBB was observed. CONCLUSIONS: In this study, participants with type 2 diabetes are at an increased risk of cardiac conduction disease but not associated with the development of right BBB.

Adipocyte dysfunction promotes lung inflammation and aberrant repair: a potential target of COPD.

Background: Obesity and chronic obstructive pulmonary disease (COPD) are prevailing worldwide, bringing a heavy medical burden. Clinical and pathophysiological relationship between obesity and COPD is paradoxical and elusive. We aim to explore their inherent associations from clinical, genetic, and animal levels. Methods: We performed literature review and cohort analysis of patients with COPD to compare lung function, symptom, and prognosis among different weight groups. After retrieving datasets of obesity and COPD in Gene Expression Omnibus (GEO) database, we carried out differentially expressed gene analysis, functional enrichment, protein-protein interactions network, and weighted gene co-expression network analysis. Then, we acquired paraffin-embedded lung tissues of fatty acid-binding protein 4-Cre-BMPR2fl/fl conditional knockout (CKO) mice that were characterized by adipocyte-specific knockout of bone morphogenetic protein receptor 2 (BMPR2) for staining and analysis. Results: Our cohort study reports the effect of obesity on COPD is inconsistent with previous clinical studies. Lung function of overweight group was statistically superior to that of other groups. We also found that the inflammatory factors were significantly increased hub genes, and cytokine-associated pathways were enriched in white adipose tissue of patients with obesity. Similarly, injury repair-associated genes and pathways were further enhanced in the small airways of patients with COPD. CKO mice spontaneously developed lung injury, emphysema, and pulmonary vascular remodeling, along with increased infiltration of macrophages. BMPR2-defiecient adipocytes had dysregulated expression of adipocytokines. Conclusion: Inflammation and abnormal repair might be potential mechanisms of the pathological association between obesity and COPD. BMPR2-associated adipocyte dysfunction promoted lung inflammation and aberrant repair, in which adipocytokines might play a role and thus could be a promising therapeutic target.

Transitions in Metabolic Health and Onset Age of Cardiovascular Diseases.

INTRODUCTION: The cardiometabolic risk associated with metabolically healthy obesity remains the subject of debate. It is unclear whether changes in metabolically healthy obesity status affect premature cardiovascular disease (CVD) risk. Authors aimed to investigate the association of metabolically healthy obesity and its transition over time with incident CVD by age at onset. METHODS: In a community-based, prospective cohort study, 54,441 adults without CVD in or before 2010 were followed for incident CVD until 2020. This sample was analyzed in 2022. Four age groups were examined (<55, 55-65, 65-75, and ≥75 years) for CVD onset. In each age group, participants were cross-classified by BMI categories and metabolic health. The Cox proportional hazards model with age as the underlying time scale was used to examine the associations of metabolic health status and its transition with CVD across BMI categories. RESULTS: During a median follow-up of 9.59 years, 3,038 participants developed CVD. Individuals with metabolically unhealthy obesity at baseline had the highest hazard ratio for CVD onset at any age, ranging from 2.68 (95% CI=2.02, 3.55) for CVD onset in those aged <55 years to 1.55 (95% CI=1.09, 2.10) for CVD onset in those aged ≥75 years. Individuals who had metabolically healthy obesity at baseline or even remained metabolically healthy during 2006-2010 were still at increased risk of premature CVD, and the association attenuated with increasing age of CVD onset. CONCLUSIONS: The metabolically healthy obesity phenotype is dynamic and its transition to a metabolically unhealthy phenotype or even stable metabolically healthy obesity is associated with an increased risk of CVD. The associations were more evident for CVD onset at younger ages.

Prevalence and clinical characteristics of atrial fibrillation in hospitalized patients with coronary artery disease and hypertension: a cross-sectional study from 2008 to 2018.

BACKGROUND: The clinical characteristics of patients with the comorbidities of hypertension and coronary artery disease (HT-CAD) and atrial fibrillation (AF) are largely unknown. This study aimed to investigate the prevalence of AF in patients with HT-CAD and clinical characteristics of patients with both HT-CAD and AF. METHODS: This cross-sectional study was conducted in Chinese People's Liberation Army General Hospital in Beijing, China, and included 20,747 inpatients with HT-CAD with or without AF from August 2008 to July 2018. We examined the overall prevalence, clinical characteristics, comorbidity profiles, treatment patterns, and blood pressure (BP) control of patients with both HT-CAD and AF. Multivariate logistic regression was used to investigate the associations of cardiovascular risk factors with AF in patients with HT-CAD. RESULTS: The overall prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747), and this increased with age; to be specific, the prevalence in women and men increased from 0.78% (2/255) and 1.02% (26/2561) at the age of <50 years to 8.73% (193/2210) and 10.28% (298/2900) at the age of ≥70 years, respectively. HT-CAD patients who had AF had a higher prevalence of cardiovascular-related comorbidities than those without AF. Multivariate logistic regression showed that age, gender (male), body mass index, heart failure, and chronic kidney disease were independently associated with the risk of AF in patients with HT-CAD. For those with both HT-CAD and AF, 73.49% (743/1011) had a CHA 2 DS 2 -VASc score of ≥4, and only about half of them had the BP controlled at <140/90 mmHg, which indicated a high risk of thromboembolism and stroke. The use of oral anticoagulation increased during the study period (10.00% [20/200] in 2008 to 2011 vs. 30.06% [159/529] in 2015 to 2018, P  < 0.01), but remained at a relatively low level. CONCLUSIONS: AF is highly prevalent among patients with HT-CAD. Patients with both HT-CAD and AF have a higher prevalence of cardiovascular-related comorbidities, lower BP control rate, and lower use of oral anticoagulation.

Single-cell analysis of peripheral blood from high-altitude pulmonary hypertension patients identifies a distinct monocyte phenotype.

Immune and inflammatory responses have an important function in the pathophysiology of pulmonary hypertension (PH). However, little is known about the immune landscape in peripheral circulation in patients with high-altitude pulmonary hypertension (HAPH). We apply single-cell transcriptomics to characterize the monocytes that are significantly enriched in the peripheral blood mononuclear cells (PBMC) of HAPH patients. We discover an increase in C1 (non-classical) and C2 (intermediate) monocytes in PBMCs and a decrease in hypoxia-inducible transcription factor-1α (HIF-1α) in all monocyte subsets associated with HAPH. In addition, we demonstrate that similar immune adaptations may exist in HAPH and PH. Overall, we characterize an immune cell atlas of the peripheral blood in HAPH patients. Our data provide evidence that specific monocyte subsets and HIF-1α downregulation might be implicated in the pathogenesis of HAPH.

Feeder cells treated with ethanol can be used to maintain self-renewal and pluripotency of human pluripotent stem cells.

Feeder cells play an important role in the culture of human pluripotent stem cells (hPSCs) in vitro. Previously, we used methanol as a fixative to prepare feeder cells for the cultivation of pluripotent stem cells (PSCs), and this method could maintain the self-renewal and pluripotency of PSCs. However, methanol is toxic, and so here we examined whether ethanol could be used to prepare feeder cells as a fixative for hPSC culturing. Primed, naïve, and extended human embryonic stem cells and induced pluripotent stem cells can maintain self-renewal and undifferentiated potential on feeder cells treated with ethanol for an extended period. RNA sequencing analysis showed that the expression of collagen-related genes in hPSCs cultured on feeder cells treated with ethanol was significantly lower as compared with hPSCs cultured on feeder cells treated with mitomycin C. Therefore, we speculate that the signaling pathway mediated by collagen-related genes may, at least in part, contribute to the maintenance of self-renewal and pluripotency of PSCs induced by feeder cells treated with chemicals.

Combined effect of inter-arm systolic blood pressure difference and carotid artery plaque on cardiovascular diseases and mortality: A prospective cohort study.

Objectives: Previous studies have confirmed the relations between inter-arm systolic blood pressure difference (IASBPD) and carotid artery plaque with the risk of cardiovascular diseases (CVD). But it is unclear whether the combined effect of IASBPD and carotid artery plaque further increases the risk of CVD and all-cause mortality. Materials and methods: We enrolled 4,970 participants (≥40 years old) in the prospective Kailuan study. All participants underwent dual-arm blood pressure and carotid artery ultrasounds. IASBPD was the absolute value of the difference between dual-arm blood pressure. All the participants were divided into four groups according to their IASBPD levels and the presence or absence of carotid artery plaque and Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident CVD and all-cause mortality. Results: During a median follow-up of 7 years, 179 CVD events and 266 deaths occurred. Multivariable Cox Regression showed that participants with IASBPD ≥ 10 mmHg and plaque had a significantly higher incidence of CVD, cerebral infarction (CI), and myocardial infarction (10, 7.27, and 1.36%, respectively). After adjusting for covariates, the IASBPD ≥ 10 mmHg and carotid plaque group significantly increased risks for CVD (HR 2.38; 95% CI, 1.40∼4.05), CI (HR, 2.47; 95% CI, 1.31∼4.67), and all-cause mortality (HR, 2.08; 95% CI, 1.20∼3.59). Conclusion: Our study indicated that the combination of IASBPD and carotid artery plaque was associated with incident CVD and all-cause mortality.

Visit-to-visit SBP variability and risk of atrial fibrillation in middle-aged and older populations.

OBJECTIVE: We sought to examine the relationship between visit-to-visit variability of SBP and incident atrial fibrillation in middle-aged and older population. METHODS: This prospective cohort study included 26 999 participants aged 50 years or older at study entry. Visit-to-visit variability of SBP was defined as the average real variability (ARV) of three values of SBP from the examinations of 2006, 2008, and 2010. We categorized participants into four groups according to the quartiles of ARV. Incident atrial fibrillation cases were identified via ECG during biennial resurveys, and reviewing medical insurance record and discharge registers. We used Cox regression models to evaluate the hazard ratios and 95% confidence intervals (CI) for incident atrial fibrillation. RESULTS: After an average follow-up of 9.24 years, a total of 420 atrial fibrillation cases were identified. The incidence of atrial fibrillation from the lowest to the highest quartiles of SBP variability were 1.23, 1.53, 1.81 and 2.19 per 1000 person-years, respectively. After adjusting for potential confounders, including mean blood pressure, we found a graded association between SBP variability and risk of atrial fibrillation. Participants in the third quartile and the highest quartile were associated with 35 and 53% higher risk of developing atrial fibrillation, respectively, compared with participants in the lowest quartile [hazard ratio (95% CI), 1.35 (1.01-1.82) and 1.53 (1.15-2.04)]. The results persisted across sensitivity analyses. CONCLUSION: Increased visit-to-visit variability of SBP is a strong predictor of incident atrial fibrillation in middle-aged and older population. Evaluation of long-term SBP variability could help to identify individuals at higher risk of atrial fibrillation.

High-Efficiency Continuous-Luminescence-Controllable Performance and Antithermal Quenching in Bi3+-Activated Phosphors.

Recently, Bi3+-activated phosphors have been widely researched for phosphor-converted light-emitting diode (pc-LED) applications. Herein, novel full-spectrum A3BO7:Bi3+ (A = Gd, La; B = Sb, Nb) phosphors with a luminescence-tunable performance were achieved by a chemical substitution strategy. In the La3SbO7 host material, a new luminescent center was introduced, with Gd3+ replacing La3+. The photoluminescence (PL) spectra show a large blue shift from 520 to 445 nm, thus achieving regulation from green to blue lights. Moreover, a series of solid solution-phase phosphors La3Sb1-xNbxO7:Bi3+ were prepared by replacing Sb with Nb, and a PL spectral tunability from green (520 nm) to orange-red (592 nm) was realized. Temperature-dependent PL spectra show that La3-xGdxSbO7:Bi3+ phosphors have excellent thermal stability. Upon 350 nm excitation, the PL intensity of La3-xGdxSbO7:Bi3+ phosphors at 150 °C remained at more than 93% at room temperature. With Gd3+ doping, the thermal stability gradually improved, and LaGd2SbO7:0.03Bi3+ represents splendid antithermal quenching (135.2% at 150 °C). Finally, a full-visible spectrum for pc-LED with a high color-rendering index (Ra = 94.4) was obtained. These results indicated that chemical substitution is an effective strategy to adjust the PL of Bi3+, which is of great significance in white-light illumination and accurate plant lighting.

Next-generation sequencing identified a novel CACNA1A I1379F variant in a familial hemiplegic migraine type 1 pedigree: A case report.

RATIONALE: Familial hemiplegic migraine (FHM) is a rare, autosomal dominant migraine with aura. CACNA1A encodes the α1A subunit of P/Q-type voltage-gated calcium channels, and its mutations have been associated with a wide spectrum of episodic and chronic neurological disorders, including FHM type 1 (FHM1). PATIENT CONCERNS: A Chinese girl and some of her relatives who presented with hemiplegia with or without migraine were found to carry a novel heterozygous missense variant, I1379F, in CACNA1A by whole-exome sequencing. The variant consegregated with the disease and was predicted to be pathogenic. DIAGNOSIS: The patient was diagnosed with FHM1 clinically and genetically. INTERVENTIONS: Prophylactic therapy with flunarizine 5 mg daily was prescribed to the patient. OUTCOMES: Therapy with flunarizine was terminated after a few weeks. The intensity of the attacks was the same as before. LESSONS: This case indicates that FHM should be considered when a patient manifests with episodic hemiplegia without migraine. In addition, genetic testing is an indispensable method to identify atypical attacks of hemiplegic migraine.

Frequency of Visit-to-Visit Variability of Resting Heart Rate and the Risk of New-Onset Atrial Fibrillation in the General Population.

Resting heart rate (RHR) has been an established predictor for atrial fibrillation (AF). However, the association of visit-to-visit heart rate variability (VVHRV) with new-onset AF risk over long term remains unclear. Our study investigates the relation of VVHRV to new-onset AF in general population in the prospective study of the Kailuan cohort. A total of 46,126 individuals without arrhythmia were included. They underwent 3 health examinations from 2006 to 2010 and performed follow up. VVHRV was measured by coefficient of variation (CV), variability independent of the mean (VIM), and standard deviation (SD). Participants were separately divided into 5 categories by quintiles of visit-to-visit RHR-CV, RHR-VIM and RHR-SD. Multivariate Cox regression and restricted cubic spline models were performed to establish the association between VVHRV and new-onset AF. 241 new-onset AF occurred during a median follow-up of 7.54 years. The incidence of new-onset AF in the group of the lowest (Q1) and highest quintiles (Q5) of RHR-CV were higher than that in other groups. The HRs for the new-onset AF were 2.07 (95% CI, 1.34-3.21, p < 0.01), in the highest quintile group(Q5) compared with group Q2, and 1.89(95% CI, 1.20-2.97, p < 0.01) in the lowest quintile group(Q1) compared with group Q2. The risk for new-onset AF showed a similar trend using RHR-VIM (p < 0.01) and RHR-SD (p < 0.05) parameters. Further sensitivity analyses indicated the consistent results in subjects without prior cardiovascular disease and without taking beta blockers or CCB. To match the covariates, analyses were also performed by propensity score matching, and prominent trends were also found in RHR-SD and RHR-VIM. In conclusion, the study indicated that higher and lower VVHRV were associated with the increasing risk of new-onset AF, which supporting a U-shaped curve existence.

Combined effect of visit-to-visit variations in heart rate and systolic blood pressure on all-cause mortality in hypertensive patients.

Elevated resting heart rate (RHR) and systolic blood pressure (SBP) are independent risk factors for all-cause mortality in hypertensive patients. However, the association of the visit-to-visit variation (VVV) in SBP and RHR with the risk of mortality in hypertensive patients remains unknown. The aim of this study was to investigate the effects of the VVVs in SBP and RHR on the risk of all-cause mortality. We enrolled 16,602 hypertensive patients from the Kailuan cohort study who underwent three health examinations from 2006 to 2010. The VVVs in SBP and RHR were defined by the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability parameters (e.g., a score of 2 indicated high variability in two parameters). Cox proportional hazards models were used to estimate hazard ratios for mortality. High VVVs in SBP and RHR were associated with an increased risk of all-cause mortality in hypertensive patients. In the multivariable-adjusted model comparing a score of 0 with a score of 2, the hazard ratios (95% confidence intervals (CIs)) for all-cause mortality were 1.38 (1.11-1.69), 1.52 (1.24-1.87), 1.32 (1.07-1.63), and 1.43 (1.16-1.75) using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability, respectively. High VVVs in SBP and RHR constituted an independent risk factor for all-cause mortality in hypertensive patients. High VVVs in SBP and RHR additively increased the risk of all-cause mortality in hypertensive patients.