Diagnostic performance of angiography-derived fractional flow reserve analysis based on bifurcation fractal law for assessing hemodynamic significance of coronary stenosis.

OBJECTIVES: Blood flow into the side branch affects the calculation of coronary angiography-derived fractional flow reserve (FFR), called Angio-FFR. Neglecting or improperly compensating for the side branch flow may decrease the diagnostic accuracy of Angio-FFR. This study aims to evaluate the diagnostic accuracy of a novel Angio-FFR analysis that considers the side branch flow based on the bifurcation fractal law. METHODS: A one-dimensional reduced-order model based on the vessel segment was used to perform Angio-FFR analysis. The main epicardial coronary artery was divided into several segments according to the bifurcation nodes. Side branch flow was quantified using the bifurcation fractal law to correct the blood flow in each vessel segment. In order to verify the diagnostic performance of our Angio-FFR analysis, two other computational methods were taken as control groups: (i) FFR_s: FFR calculated by delineating the coronary artery tree to consider side branch flow, (ii) FFR_n: FFR calculated by just delineating the main epicardial coronary artery and neglecting the side branch flow. RESULTS: The analysis of 159 vessels from 119 patients showed that our Anio-FFR calculation method had comparable diagnostic accuracy to FFR_s and provided significantly higher diagnostic accuracy than that of FFR_n. In addition, using invasive FFR as a reference, the Pearson correlation coefficients of Angio-FFR and FFRs were 0.92 and 0.91, respectively, while that of FFR_n was only 0.85. CONCLUSIONS: Our Angio-FFR analysis has demonstrated good diagnostic performance in assessing the hemodynamic significance of coronary stenosis by using the bifurcation fractal law to compensate for side branch flow. CLINICAL RELEVANCE STATEMENT: Bifurcation fractal law can be used to compensate for side branch flow during the Angio-FFR calculation of the main epicardial vessel. Compensating for side branch flow can improve the ability of Angio-FFR to diagnose stenosis functional severity. KEY POINTS: • The bifurcation fractal law could accurately estimate the blood flow from the proximal main vessel into the main branch, thus compensating for the side branch flow. • Angiography-derived FFR based on the bifurcation fractal law is feasible to evaluate the target diseased coronary artery without delineating the side branch.

Association between admission plasma 2-oxoglutarate levels and short-term outcomes in patients with acute heart failure: a prospective cohort study.

BACKGROUND: 2-oxoglutarate (2OG), an intermediate metabolite in the tricarboxylic acid cycle, has been found to associate with chronic heart failure (HF), but its effect on short-term adverse outcomes in patients with acute HF (AHF) is uncertain. METHODS: This prospective cohort study included 411 consecutive hospitalized patients with AHF. During hospitalization, fasting plasma samples were collected within the first 24 h of admission. Plasma 2OG levels were measured by hydrophilic interaction liquid chromatography-liquid chromatography tandem mass spectrometry (HILIC-LC/MS/MS). All participants were followed up for six months. Multiple logistic regression was used to determine the odds ratio (OR) and 95% confidence interval (CI) for primary outcomes. RESULTS: The AHF cohort consisted of HF with preserved ejection fraction (EF) (64.7%), mid-range EF (16.1%), and reduced EF (19.2%), the mean age was 65 (±13) years, and 65.2% were male. Participants were divided into two groups based on median 2OG levels (µg/ml): low group (< 6.0, n = 205) and high group (≥6.0, n = 206). There was a relatively modest correlation between 2OG and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels (r = 0.25; p < 0.001). After adjusting for age, sex, and body mass index, we found that the progression of the NYHA classification was associated with a gradual increase in plasma 2OG levels (p for trend< 0.001). After six months of follow-up, 76 (18.5%) events were identified. A high baseline 2OG level was positively associated with a short-term rehospitalization and all-cause mortality (OR: 2.2, 95% CI 1.3-3.7, p = 0.003), even after adjusting for NT-proBNP and estimated glomerular filtration rate (eGFR) (OR: 1.9, 95% CI 1.1-3.4, p = 0.032). After a similar multivariable adjustment, the OR was 1.4 (95% CI 1.1-1.7, p = 0.018) for a per-SD increase in 2OG level. CONCLUSIONS: High baseline 2OG levels are associated with adverse short-term outcomes in patients with AHF independent of NT-proBNP and eGFR. Hence plasma 2OG measurements may be helpful for risk stratification and treatment monitoring in AHF. TRIAL REGISTRATION: ChiCTR-ROC-17011240 . Registered 25 April 2017.

ß-blockers and risk of all-cause mortality in patients with chronic heart failure and atrial fibrillation-a meta-analysis.

BACKGROUND: Effects of ß-blockers on outcomes in patients with chronic heart failure (CHF) and atrial fibrillation (AF) is still in controversy. METHODS: Searching was conducted by using keywords "atrial fibrillation", and "heart failure" in PubMed, MEDLINE and Embase databases before November 30, 2017. Prospective studies [i.e. randomized control trials (RCTs), post-hoc analysis of RCTs, prospective cohort studies and registry studies] that studied the effect of ß-blockers and all-cause mortality in patients with CHF and AF were included. The analysis was stratified by study design. RESULTS: We identified 12 studies, including 6 post-hoc analysis of RCTs and 6 observational studies (including prospective registry studies and prospective cohort studies), which enrolled 38,133 patients with CHF and AF. Overall, ß-blockers treatment was associated with significant decrease in all-cause mortality [Risk Ratio (RR) =0.73; 95% Confidence Interval (CI) 0.65-0.82, P < 0.001]. When stratified by study design, ß-blockers treatment was associated with 34% reduction in patients with CHF and AF in observational study (RR = 0.66; 95% CI 0.58-0.76, P < 0. 001), but not in post-hoc analysis of RCT (RR = 0.87; 95% CI 0.74-1.02, P = 0.09). CONCLUSIONS: ß-blockers treatment was associated with significantly decrease the risk of all-cause mortality in patients with AF-CHF and it was only seen in observational study group, but not in subgroup analysis of RCT group. Further large RCTs are required to verify the effect of ß-blockers treatment on patients with CHF and AF. The main limitation of this study is the lack of individual data on patients in each study.

Acetyl-CoA-dependent ac4C acetylation promotes the osteogenic differentiation of LPS-stimulated BMSCs.

The impaired osteogenic capability of bone marrow mesenchymal stem cells (BMSCs) caused by persistent inflammation is the main pathogenesis of inflammatory bone diseases. Recent studies show that metabolism is disturbed in osteogenically differentiated BMSCs in response to Lipopolysaccharide (LPS) treatment, while the mechanism involved remains incompletely revealed. Herein, we demonstrated that BMSCs adapted their metabolism to regulate acetyl-coenzyme A (acetyl-CoA) availability and RNA acetylation level, ultimately affecting osteogenic differentiation. The mitochondrial dysfunction and impaired osteogenic potential upon inflammatory conditions accompanied by the reduced acetyl-CoA content, which in turn suppressed N4-acetylation (ac4C) level. Supplying acetyl-CoA by sodium citrate (SC) addition rescued ac4C level and promoted the osteogenic capacity of LPS-treated cells through the ATP citrate lyase (ACLY) pathway. N-acetyltransferase 10 (NAT10) inhibitor remodelin reduced ac4C level and consequently impeded osteogenic capacity. Meanwhile, the osteo-promotive effect of acetyl-CoA-dependent ac4C might be attributed to fatty acid oxidation (FAO), as evidenced by activating FAO by L-carnitine supplementation counteracted remodelin-induced inhibition of osteogenesis. Further in vivo experiments confirmed the promotive role of acetyl-CoA in the endogenous bone regeneration in rat inflammatory mandibular defects. Our study uncovered a metabolic-epigenetic axis comprising acetyl-CoA and ac4C modification in the process of inflammatory osteogenesis of BMSCs and suggested a new target for bone tissue repair in the context of inflammatory bone diseases.

The m6A eraser FTO suppresses ferroptosis via mediating ACSL4 in LPS-induced macrophage inflammation.

Acute lung injury (ALI) is a serious disorder characterized by the release of pro-inflammatory cytokines and cascade activation of macrophages. Ferroptosis, a form of iron-dependent cell death triggered by intracellular phospholipid peroxidation, has been implicated as an internal mechanism underlying ALI. In this study, we investigated the effects of m6A demethylase fat mass and obesity-associated protein (FTO) on the inhibition of macrophage ferroptosis in ALI. Using a mouse model of lipopolysaccharide (LPS)-induced ALI, we observed the induction of ferroptosis and its co-localization with the macrophage marker F4/80, suggesting that ferroptosis might be induced in macrophages. Ferroptosis was promoted during LPS-induced inflammation in macrophages in vitro, and the inflammation was counteracted by the ferroptosis inhibitor ferrostatin-1 (fer-1). Given that FTO showed lower expression levels in the lung tissue of mice with ALI and inflammatory macrophages, we further dissected the regulatory capacity of FTO in ferroptosis. The results demonstrated that FTO alleviated macrophage inflammation by inhibiting ferroptosis. Mechanistically, FTO decreased the stability of ACSL4 mRNA via YTHDF1, subsequently inhibiting ferroptosis and inflammation by interrupting polyunsaturated fatty acid consumption. Moreover, FTO downregulated the synthesis and secretion of prostaglandin E2, thereby reducing ferroptosis and inflammation. In vivo, the FTO inhibitor FB23-2 aggravated lung injury, the inflammatory response, and ferroptosis in mice with ALI; however, fer-1 therapy mitigated these effects. Overall, our findings revealed that FTO may function as an inhibitor of the inflammatory response driven by ferroptosis, emphasizing its potential as a target for ALI treatment.

CALCRL Gene is a Suitable Prognostic Factor in AML/ETO+ AML Patients.

Introduction: The t(8 ; 21) translocation is the most common chromosomal abnormality in human acute myeloid leukemia (AML) subtype 2 (M2), which forms the AML/ETO fusion gene. However, AML/ETO alone does not necessarily cause leukemia. Other factors are thought to contribute to the disease. Calcitonin receptor-like (CALCRL), a G-protein-coupled neuropeptide receptor, is involved in various biological processes, such as colony formation and drug resistance. Methods: First, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to determine any differences in CALCRL expression in AML patients with and without AML/ETO and the prognostic significance of CALCRL expression in AML patients was further evaluated. Next, we detected the CALCRL expression level in 67 AML/ETO+ AML patients and 16 patients with nonmalignant hematological diseases using qRT-PCR and identified its prognostic relevance. Results: Individuals in the group expressing low levels of CALCRL had a longer median survival time. In AML/ETO+ AML patients, higher mRNA levels of CALCRL were observed before treatment, which decreased after the complete remission that followed multiple chemotherapy sessions. Clinical features indicated that more patients in the CALCRLhigh group also had c-kit mutations compared with patients in other groups. Overall survival (OS) was longer in patients with lower levels of CALCRL expression, especially in patients with c-kit mutations or with more blast cells in bone marrow (BM). In addition, a longer OS was observed in the CALCRLlow group after hematopoietic stem cell transplantation (HSCT). Conclusions: This preliminary study indicates that CALCRL could serve as a suitable prognostic factor in AML/ETO+ AML patients.

H22954, a long non-coding RNA, inhibits glucose uptake in leukemia cells in a GLUT10-dependent manner.

OBJECTIVES: To investigate the performance of H22954, a novel long non-coding RNA (lncRNA), in inhibiting glucose uptake in leukemia cells. METHODS: 18F-FDG uptake, RNA half-life quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase assays were performed to detect the glucose uptake in the condition of leukemia. Microarrays and qRT-PCR analyses were used to identify the related genes or proteins and elucidate the underlying these processes. RESULTS: H22954, a novel lncRNA, inhibited glucose uptake in leukemia cells. Using bioinformatics and microarray analyses, GLUT10 was identified as a possible target molecule of H22954. H22954 targeted the 3'untranslated region of GLUT10. In the luciferase assay, the luciferase activity of pGL3-GLUT10 was inhibited by H22954. Consistently, H22954 expression levels were inversely correlated with GLUT10 expression in cell lines and acute myeloid leukemia (AML) samples. Conversely, the degradation rate of GLUT10 mRNA was increased after H22954 overexpression. Moreover, glucose uptake was recovered when the GLUT10-interaction sites in H22954 were mutated. CONCLUSION: The lncRNA H22954 regulated GLUT10 expression to inhibit glucose uptake in leukemia cells. Our findings provide potentially valuable data for designing new targeted strategies based on H22954.

Effect of Hypertension Duration and Blood Pressure Control During Early Adulthood on Cognitive Function in Middle Age.

BACKGROUND: Elevated blood pressure (BP) is a risk factor for cognitive impairment. OBJECTIVE: We aim to explore the association between the duration of hypertension in early adulthood, with cognitive function in midlife. Furthermore, we investigate whether this asssociation is altered among participants with controlled BP. METHODS: This prospective study included 2,718 adults aged 18-30 years without hypertension at baseline who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Duration of hypertension was calculated based on repeat measurements of BP performed at 2, 5, 7, 10, 15, 20, and 25 years after baseline. Cognitive function was assessed at Year-25 using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Stroop test. RESULTS: After multivariable adjustment, a longer hypertension duration was associated with worse verbal memory (RAVLT, p trend = 0.002) but not with processing speed (DSST, p trend = 0.112) and executive function (Stroop test, p trend = 0.975). Among subgroups of participants with controlled (BP < 140/90 mmHg) and uncontrolled (SBP≥140 mmHg or DBP≥90 mmHg) BP at the time of cognitive assessment (i.e., Year-25 BP), longer duration of hypertension was associated with worse verbal memory. Similar results were observed in subgroups with controlled and uncontrolled average BP prior to cognitive assessment. CONCLUSION: Longer duration of hypertension during early adulthood is associated with worse verbal memory in midlife regardless of current or long-term BP control status. The potential risk of hypertension associated cognitive decline should not be overlooked in individuals with a long duration of hypertension, even if BP levels are controlled.

Analysis of a machine learning-based risk stratification scheme for acute kidney injury in vancomycin.

Vancomycin-associated acute kidney injury (AKI) continues to pose a major challenge to both patients and healthcare providers. The purpose of this study is to construct a machine learning framework for stratified predicting and interpreting vancomycin-associated AKI. Our study is a retrospective analysis of medical records of 724 patients who have received vancomycin therapy from 1 January 2015 through 30 September 2020. The basic clinical information, vancomycin dosage and days, comorbidities and medication, laboratory indicators of the patients were recorded. Machine learning algorithm of XGBoost was used to construct a series risk prediction model for vancomycin-associated AKI in different underlying diseases. The vast majority of sub-model performed best on the corresponding sub-dataset. Additionally, the aim of this study was to explain each model and to explore the influence of clinical variables on prediction. As the results of the analysis showed that in addition to the common indicators (serum creatinine and creatinine clearance rate), some other underappreciated indicators such as serum cystatin and cumulative days of vancomycin administration, weight and age, neutrophils and hemoglobin were the risk factors for cancer, diabetes mellitus, heptic insufficiency respectively. Stratified analysis of the comorbidities in patients with vancomycin-associated AKI further confirmed the necessity for different patient populations to be studied.

Visit-to-Visit Fasting Glucose Variability in Young Adulthood and Nonalcoholic Fatty Liver Disease in Middle Age.

CONTEXT: Diabetes has a bidirectional association with nonalcoholic fatty liver disease (NAFLD) and increases the risk of cirrhosis and related complications. OBJECTIVE: To investigate the association between visit-to-visit fasting glucose (FG) variability in early adulthood and NAFLD in middle age. METHODS: This prospective cohort study included 2467 Black and White adults aged 18 to 30 years at baseline (1985-1986) who were followed over 25 years in the Coronary Artery Risk Development in Young Adults Study. FG variability measures included coefficient of variation about the mean FG (CV-FG), the SD of FG (SD-FG), and the average real variability of FG (ARV-FG) across 25 years (year 0, 7, 10, 15, 20, and 25 examinations). NAFLD was defined as liver attenuation ≤ 40 Hounsfield units on computed tomography scan at year 25 examination after excluding other causes of hepatic steatosis. RESULTS: Of the 2467 participants, 241 (9.8%) had NAFLD at year 25. In multivariate analysis, the odds ratio for NAFLD was 2.80 (95% CI, 1.69-4.64; P trend < 0.001) for the fourth quartile vs first quartile of CV-FG after adjusting for confounding variables, including mean FG. Similar results were observed for SD-FG and ARV-FG. CONCLUSION: Greater visit-to-visit FG variability in early adulthood was associated with higher risk of NAFLD in middle age independent of mean FG level. FG variability may help identify individuals at high risk for NAFLD.

Blood pressure trajectories in early adulthood and myocardial structure and function in later life.

AIMS: This study sought to investigate the association between blood pressure (BP) trajectories from early to middle adulthood and echocardiographic indices of structure and function in middle age. METHODS AND RESULTS: This prospective cohort study included 4717 black and white adults aged 18-30 years at baseline (1985-86) who were followed over 30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Trajectories of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) from the Year 0 examination to Year 30 examination were identified using latent mixture modelling. Echocardiographic indices of myocardial structure, systolic function, and diastolic function were assessed at the Year 30 examination. Five distinct SBP trajectory groups were identified: low-stable [1110 participants (23.5%)], moderate-stable [2188 (46.4%)], high-stable [850 (18.0%)], moderate-increasing [416 (8.8%)], and high-increasing [153 (3.2%)]. After adjustment for clinical variables, a significant decreasing trend was observed from the high-increasing and moderate-increasing groups through to the low-stable group for left ventricular (LV) mass index [mean (SE): high-increasing, 112.3 (3.4); moderate-increasing, 99.3 (2.6); high-stable, 88.9 (2.5); moderate-stable, 86.1 (2.3); low-stable, 82.1 (2.4), P trend < 0.01], as well as LV end-diastolic dimension, left atrial volume index, and E/e', while an increasing trend was apparent for LV longitudinal strain, E/A ratio, and average e' velocities. Results were generally consistent for trajectories of DBP and PP. CONCLUSIONS: Higher BP trajectories from early to middle adulthood were associated with worse indices of myocardial modelling and LV systolic and diastolic function at middle age.

Triglyceride-Glucose Index and Homeostasis Model Assessment-Insulin Resistance in Young Adulthood and Risk of Incident Congestive Heart Failure in Midlife: The Coronary Artery Risk Development in Young Adults Study.

Objective: This study aimed to assess the association between triglyceride-glucose (TyG) index/homeostasis model assessment-insulin resistance (HOMA-IR) within young adults and congestive heart failure (CHF), and to explore whether TyG index can replace HOMA-IR as a surrogate marker for IR in predicting the risk of CHF. Methods: A total of 4,992 participants between the ages of 18 and 30 years were enrolled from the Coronary Artery Risk Development in Young Adults (CARDIA) investigation [from 1985 to 1986 (year 0)]. A Cox proportional hazard regression analysis was conducted for assessing correlations between baseline TyG index/HOMA-IR and CHF events, together with the receiver operating characteristic (ROC) curve employed for scrutinizing TyG index/HOMA-IR and the risk of CHF. Results: During the 31-year follow-up period, 64 (1.3%) of the 4,992 participants developed CHF. In multivariable Cox proportional hazards models, adjusted for confounding factors for CHF, an increased risk of CHF was associated with a per-unit increase in the TyG index [hazard ratio (HR) 2.8; 95% confidence interval (CI), 1.7-4.7] and HOMA-IR (HR 1.2; 95% CI, 1.1-1.3). A Kaplan-Meier curve analysis showed that participants in the TyG index and HOMA-IR index Q4 group had a higher risk of CHF than those in the Q1 group. The area under curve (AUC) for the TyG index and HOMA-IR consisted of 0.67 (95% CI, 0.6-0.742) and 0.675 (95% CI, 0.604-0.746), respectively. There were no significant differences between the TyG index and HOMA-IR for AUC (p = 0.986). Conclusion: The higher TyG index and HOMA-IR are independent risk factors for CHF. The TyG index can replace HOMA-IR in young adulthood as a surrogate marker for IR to predict the risk of CHF.

Heart Failure Is Associated with Increased Risk of Long-Term Venous Thromboembolism.

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), is highly prevalent in in-hospital HF patients and contributes to worse prognoses. However, the risk of VTE in out-patients with HF in long-term period is controversial. This study aimed to evaluate the associations between HF and the risk of VTE in a long-term follow-up duration. METHODS: We searched for studies investigating the risk of VTE, PE, and DVT in patients with HF before April 15, 2020, in PubMed, MEDLINE, and Embase databases. Cohort studies and post hoc analysis of RCTs were eligible for inclusion if they reported relative risk of VTE, DVT or PE in patients with HF in more than 3-month follow-up period. RESULTS: We identified 31 studies that enrolled over 530,641 HF patients. Overall, patients with HF were associated with an increased risk of VTE (risk ratio [RR]=1.57, 95% confidence interval [CI]=1.34-1.84) and PE (RR=2.00, 95% CI=1.38-2.89). However, the risk of DVT was not significantly increased in HF patients (RR=1.33, 95% CI=0.67-2.63). Subgroup analysis showed that patients with chronic HF (RR=1.54, 95% CI=1.32-1.80) had a higher risk of VTE than those with acute HF (RR=0.95, 95% CI=0.68-1.32). CONCLUSIONS: In conclusion, HF was an independent risk for VTE and PE but not DVT in a long-term follow-up period. Patients with chronic HF were prone to suffer from VTE than acute HF.

Efficacy and safety of antithrombotic therapy with non-vitamin K antagonist oral anticoagulants after transcatheter aortic valve replacement: a systematic review and meta-analysis.

OBJECTIVE: A meta-analysis was performed to compare the efficacy and safety of antithrombotic therapy with non-vitamin K antagonist oral anticoagulants (NOACs) versus standard care in patients after successful transcatheter aortic valve replacement (TAVR). METHODS: A systematic search of PubMed, Cochrane Central Register of Controlled Trials, and EMBASE databases and ClinicalTrials.gov website (through 21 October 2020) was performed. Risk ratios (RRs) with 95% confidence intervals (CIs) for all outcomes were calculated using random-effects models. RESULTS: Twelve studies (two studies were randomized controlled trials) comprising 6943 patients were included (5299 had indications for oral anticoagulation (OAC) and 1644 had none). No significant differences were found between NOACs and the standard care in the incidences of all stroke, a composite endpoint, and major/life-threatening bleeding. NOACs were associated with lower all-cause mortality than vitamin K antagonists (VKAs) in post-TAVR patients with indications for OAC after more than 1 year of follow-up [RR = 0.64; 95% CI, (0.42, 0.96); p = 0.03], whereas NOACs exhibited poor outcomes than antiplatelet therapy (APT) in patients without indications for OAC [RR = 1.66; 95% CI, (1.12, 2.45); p = 0.01]. In the prevention of valve thrombosis, NOACs and VKAs were not significantly different in patients with indications for OAC [RR = 0.66; 95% CI, (0.24, 1.84); p = 0.43], whereas NOACs were better than APT in patients without indications for OAC [RR = 0.19; 95% CI, (0.04, 0.83); p = 0.03]. CONCLUSIONS: In patients with indications for OAC, post-TAVR antithrombotic therapy with NOACs was more favorable due to its lower all-cause mortality after more than 1 year of follow-up. In those without indications for OAC, NOACs presented poorer outcomes due to its higher all-cause mortality.

One-year change in resting heart rate and subsequent risk of hypertension in healthy Chinese adults.

BACKGROUND: Changes in baseline resting heart rate (RHR) appear to predict new-onset hypertension (NOH). However, RHR is a dynamic anthropometric parameter; thus, the association between changes in RHR and NOH requires further investigation. METHODS: We studied 10 403 participants who were initially normotensive and who had at least one routine health examination at baseline and 1 year later during 2011-2016. We compared the RHR between the baseline and 1-year follow-up. We defined hypertension as SBP ≥140 mmHg or DBP ≥90 mmHg. Participants were divided into three groups: RHR decreased, RHR unchanged [from 0 to 10 beats per minute (bpm)], and RHR increased ≥10 bpm. Cox regression analysis was performed to calculate relative risk with 95% confidence intervals (CIs) for the association between NOH and RHR change. RESULTS: During a mean follow-up period of 2.42 years, 1173 (11.28%) participants developed hypertension. After adjusting for age, sex, SBP, DBP, RHR and other confounders obtained at baseline, and compared with participants with unchanged RHR, participants with decreased RHR had a 17% decreased risk of NOH (adjusted hazard ratio: 0.83, 95% CI 0.73-0.95), whereas subjects with RHR that increased ≥10 bpm had a 23% increased risk of NOH (adjusted hazard ratio: 1.23, 95% CI 1.04-1.46). CONCLUSION: A 1-year increase in RHR for initially normotensive subjects is an independent risk factor for subsequent hypertension.

[Clinical features of severe or critical ill patients with COVID-19].

OBJECTIVE: To analyze the clinical features of severe or critical ill adult patients with coronavirus disease (COVID-19). METHODS: The clinical data of 75 patients with severe or critical COVID-19 in Honghu People's Hospital from January to March in 2020 were collected. RESULTS: Of the 75 patients with COVID-19 pneumonia, 41 were male (54.67%) and 34 were female (45.33%) with a mean age of 67.53 ±12.37 years; 43 patients had severe and 32 had critical COVID-19, and 49.3% of the patients had underlying diseases. The main clinical manifestations included fever (78.67%) and coughing (70.67%). Compared with the severe patients, the critically ill patients had higher proportions of patients over 60 years old with elevated white blood cell count, increased prothrombin time, and higher levels of hsCRP, PCT, D-dimer, ALT, LDH, cTnI and NT-proBNP. Univariate logistic regression analysis showed that an age over 60 years, leukocytosis, hs-CRP elevation, prolonged prothrombin time, and increased levels of D-dimer, NT-proBNP and cTnI were associated with severe COVID-19. Multivariate logistic regression showed that an age over 60 years (OR=8.165, 95% CI: 1.483-45.576, P=0.017), prolonged prothrombin time (OR=7.516, 95% CI: 2.568-21.998, P=0.006) and elevated NT-proBNP (OR=6.194, 95% CI: 1.305-29.404, P=0.022) were independent risk factors for critical type of COVID-19. CONCLUSIONS: An age over 60 years, a prolonged prothrombin time and elevated NT-proBNP level are important clinical features of critically ill patients with COVID-19, and can be deemed as early warning signals for critical conditions of the disease.

Clustering of risk factors and the risk of new-onset hypertension defined by the 2017 ACC/AHA Hypertension Guideline.

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) lowered the diagnostic criteria for hypertension. We aimed to explore whether clustering of multiple risk factors are associated with the risk of new-onset hypertension defined by the 2017 ACC/AHA Hypertension Guideline. Subjects who attended ≥2 annual health examinations without baseline hypertension and cardiovascular disease were included. Hypertension was defined according to the 2017 ACC/AHA Hypertension Guideline. Seven predefined risk factors, including age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and a poor estimated glomerular filtration rate, were analyzed. A composite, individual-level, cumulative score incorporating these seven risk factors (no = 0 point; yes = 1 point; total range of 0-7 points) was calculated. The association between the cumulative score and the risk of hypertension was analyzed using a Cox regression model. A total of 4424 (21.6%) of 20,190 subjects included had new-onset hypertension during a follow-up duration of 3.6 years. Compared with subjects with 0 points, the adjusted hazard ratios (95% confidence intervals) for the development of hypertension for those with 1, 2, 3, and ≥4 points were 1.21 (1.07-1.38), 1.34 (1.19-1.52), 1.44 (1.26-1.63), and 1.64 (1.44-1.87), respectively (P < 0.001), after adjustment for sex and baseline blood pressure. Age, resting heart rate, overweight/obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and a poor estimated glomerular filtration rate are associated with an increased risk of future hypertension. When these factors are combined, there is an accumulated increase in risk.

Association of Urine Albumin/Creatinine Ratio below 30 mg/g and Left Ventricular Hypertrophy in Patients with Type 2 Diabetes.

Several studies show that even a level of urine albumin/creatinine ratio (UACR) within the normal range (below 30 mg/g) increases the risk of cardiovascular diseases. We speculate that mildly increased UACR is related to left ventricular hypertrophy (LVH) in patients with type 2 diabetes mellitus (T2DM). In this retrospective study, 317 patients with diabetes with normal UACR, of whom 62 had LVH, were included. The associations between UACR and laboratory indicators, as well as LVH, were examined using multivariate linear regression and logistic regression, respectively. The diagnostic efficiency and the optimal cutoff point of UACR for LVH were evaluated using the area under the receiver operating characteristic curve (AUC) and Youden index. Our results showed that patients with LVH had significantly higher UACR than those without LVH (P < 0.001). The prevalence of LVH presented an upward trend with the elevation of UACR. UACR was independently and positively associated with hemoglobin A1c (P < 0.001). UACR can differentiate LVH (AUC = 0.682, 95% CI (0.602-0.760), P < 0.001). The optimal cutoff point determined with the Youden index was UACR = 10.2 mg/g. When categorized by this cutoff point, the odds ratio (OR) for LVH in patients in the higher UACR group (10.2-30 mg/g) was 3.104 (95% CI: 1.557-6.188, P=0.001) compared with patients in the lower UACR group (<10.2 mg/g). When UACR was analyzed as a continuous variable, every double of increased UACR, the OR for LVH was 1.511 (95% CI: 1.047-2.180, P=0.028). Overall, UACR below 30 mg/g is associated with LVH in patients with T2DM. The optimal cutoff value of UACR for identifying LVH in diabetes is 10 mg/g.

Effect of asafoetida extract on growth and quality of Pleurotus ferulic.

Different concentrations of asafoetida extract were added to the medium of Pleurotus ferulic and the effects of the extract on growth of P. ferulic mycelium and fruiting bodies was observed. As the amount of asafoetida extract additive was increased, the growth of Pleurotus mycelium was faster, the time formation of buds was shorter and that yield of fruiting bodies was stimulated. However, overdosing of asafoetida extract hampered the growth of Pleurotus ferulic. The amino acid composition and volatile components in three kinds of pleurotus' were contrasted, including wild pleurotus (WP), cultivated pleurotus with asafoetida extract (CPAE) and cultivated pleurotus without asafoetida extract (CP). CPAE with 2.3 g/100 g asafoetida extract addition had the highest content of total amino acids, as well as essential amino acids. WP had a higher content of total amino acids and essential amino acids than CP. In addition, CPAE with 2.3 g/100 g had the highest score of protein content of pleurotus fruiting bodies, while WP had a higher score than CP. In the score of essential amino acid components of pleurotus fruiting bodies, CP had the highest score, while CPAE was higher than WP. Asafoetida extract influenced the volatile components of Pleurotus ferulic greatly, making the volatile components of cultivated pleurotus more similar to those of wild pleurotus (WP).

Catalytic Enantioselective Diels-Alder Reactions of Benzoquinones and Vinylindoles with Chiral Magnesium Phosphate Complexes.

Tetrahydrocarbazole and its derivatives have received much attention due to the prevalence of this scaffold in natural products and their use in organic synthesis. We have developed a Diels-Alder reaction of benzoquinones and 3-vinylindoles catalyzed by chiral magnesium phosphate complexes to provide tetrahydrocarbazole derivatives in excellent yields and enantioselectivities (up to >99% yield, 99% ee). This transformation features a wide substrate scope, excellent enantioselectivities, and mild conditions.