Purpose:Chronotype can be used to describe individual's circadian preference in behavioral and circadian rhythm, representing the preferences for earlier or later sleep times. This study aimed to investigate the association of chronotype with hypertension and metabolic parameters in middle-aged and older adults. Patients and Methods:A total of 945 participants were recruited from December 2023 to December 2024 at First Affiliated Hospital of University of Science and Technology of China. Chronotype was determined using the full Morningness-Eveningness Questionnaire, with higher scores indicating preference for morning chronotype. Chronotype was dichotomized at the median score in current cohort, classifying 447 participants as morning chronotypes and 498 as evening chronotypes. Anthropometric measurements and biochemical analyses were also conducted. Multivariable logistic, linear regression, and restricted cubic spline (RCS) analyses were employed to evaluate association between chronotype, metabolic parameters, and hypertension. Results:After adjustment for covariates, evening chronotype was significantly associated with hypertension risk (OR = 1.60, 95% CI: 1.17-2.17), compared with morning chronotype. The RCS analysis suggested a significant nonlinearity association between chronotype score and hypertension (P for nonlinear = 0.047). Furthermore, higher chronotype score was significantly associated with decreased levels of total cholesterol [TC, β (95% CI): -0.12 (-0.19, -0.04)], low-density lipoprotein-cholesterol [LDL-C, β (95% CI): -0.21 (-0.33, -0.08)] and serum uric acid [SUA, β (95% CI): -0.09 (-0.18, -0.01)], but with increased levels of aspartate aminotransferase [AST, β (95% CI): 0.16 (0.05, 0.27)]. In discrimination model, chronotype was associated with hypertension independently of TC, SUA, alanine transaminase, and alkaline phosphatase, with model's AUC of 0.779 (95% CI: 0.749-0.808). Conclusion:In middle-aged and older adults, preference for morning chronotype was associated with decreased levels of TC, LDL-C, and SUA, but with increased levels of AST. Moreover, evening chronotype was significantly independently associated with increased risk of hypertension.

BackgroundDecreased serum albumin level (SAL) is associated with adverse clinical outcomes. We designed the present study to further assess the prognostic value of SAL in critically ill patients based on data from large intensive care unit (ICU) databases.MethodsThis retrospective cohort study recruited 18,353 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Restricted cubic splines (RCS) were performed to visualize the association of SAL at admission with ICU and hospital mortalities. The prognostic value of SAL was analyzed using logistic regression models and receiver operating characteristic (ROC) curves in overall patients and subgroups.ResultsRestricted cubic splines revealed rapid increasing risks in ICU and hospital mortalities when SAL declined to below 30 g/l. Patients with SAL <30 g/l (n = 6,069) had higher ICU (13.7% vs. 6.4%, p < 0.001) and hospital (23.9% vs. 10.7%, p < 0.001) mortalities than those with SAL ≥30 g/l. Multivariable logistic regression model revealed that SAL <30 g/l independently correlated with higher risks of both ICU (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07–1.36) and hospital (OR: 1.51, 95% CI: 1.37–1.66) mortalities. However, the association diminished in patients with cirrhosis (OR: 1.16, 95% CI: 0.91–1.49 for ICU mortality; OR: 1.21, 95% CI: 1.00–1.48 for hospital mortality). ROC curves revealed a poor performance of SAL in predicting mortalities, both in overall patients and in those with cirrhosis.ConclusionsDecreased SAL is associated with increased risk of mortality. However, it possesses low sensitivity and specificity for outcome prediction in critically ill patients, especially in those with cirrhosis.

Abstract Background To explore the potential heterogeneity of acute kidney injury (AKI) and evaluate the prognostic differences among AKI subphenotypes in critically ill patients with cardiovascular diseases. Methods Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-III database. Latent class analysis (LCA) was used to explore the potential subphenotypes of AKI in critically ill patients with cardiovascular diseases. The number of classes was identified by the Bayesian information criterion and entropy. The differences in prognostic ability among the AKI subphenotypes were evaluated by logistic regression analysis. Result A total of 7738 AKI patients were enrolled in this study. Using LCA, AKI patients were divided into 4 heterogeneous subphenotypes, which were obviously different from the Kidney Disease: Improving Global Outcomes (KDIGO) stages. Interestingly, class 3 classified by LCA was dominated by stage 2, while the mortality rate in class 3 was significantly different from that in class 1 (15.2% vs. 1.6%, p < 0.05). After further adjustment, the mortality rate in class 3 remained higher than that in class 1, with an odds ratio of 12.31 (95% confidence interval, 8.96–16.89). Conclusions LCA was feasible for AKI classification in critically ill patients with cardiovascular disease, and 4 distinct subphenotypes of AKI patients with different prognoses were identified. Our results highlighted the potential heterogeneity of AKI patients, which is worthy of further investigation.

Background: To assess the association between serum lactate dehydrogenase (LDH) levels and mortality in intensive care unit patients. Materials & methods: A total of 1981 patients in the eICU Collaborative Research Database were divided into four groups according to quartiles of LDH levels. Logistic regressions were performed. Results: Elevated LDH levels were significantly associated with higher mortality (intensive care unit mortality: Q2 vs Q1: 1.046 [0.622-1.758]; Q3 vs Q1: 1.667 [1.029-2.699]; and Q4 vs Q1: 1.760 [1.092-2.839]). Similar results persisted in patients with different acute physiology and chronic health evaluation IV scores, and with or without sepsis. Conclusion: The serum LDH level may aid in the early identification of mortality risk in critically ill patients.

Previous studies have found a connection between left coronary artery dominance and worse prognoses in patient with acute coronary syndrome, which remains a predominant cause of morbidity and mortality globally. The aim of this study was to investigate whether coronary dominance is associated with the incidence of acute inferior myocardial infarction (MI). Between January 2011 and November 2014, 265 patients with acute inferior MI and 530 age-matched and sex-matched controls were recruited for a case-control study in the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. All participants underwent coronary angiography. The exclusion criteria included history of coronary artery bypass graft surgery, chronic or systemic diseases (including hepatic failure, kidney failure, hypothyroidism and Grave’s disease), ventricular fibrillation, and known allergy to iodinated contrast agent. Patients with left- or co-dominant anatomies were placed into the LD group and those with right-dominant anatomy were included in the RD group. The association of acute inferior MI and coronary dominant anatomy were assessed using multivariable conditional logistic regression, and to estimate the odds ratio (OR) and 95% confidence interval (95%CI). Distributions of right dominance were significantly different between the acute inferior MI group and control group (94.0% vs. 87.9%, P = 0.018). Univariable conditional logistic regression revealed that right dominance may be a risk factor for the incident acute inferior MI (OR: 2.137; 95% CI: 1.210–3.776; P = 0.009). After adjusting for baseline systolic blood pressure, heart rate, smoking status, diabetes mellitus, hypertension, hyperlipidaemia, and family history of coronary artery disease, results of multivariate conditional logistic regression showed that right dominance was associated with the incidence of acute inferior MI (OR: 2.396; 95% CI: 1.328–4.321; P = 0.004). Right coronary dominance may play a disadvantageous role in the incidence of acute inferior MI. However, further studies are needed to verify our findings, especially with regard to the underlying mechanisms.

The abnormalities of blood pressure (BP) nocturnal decline have been found to be predictive for carotid plaque and lacunar infarction in patients with hypertension. In this study, BP dipping patterns in postmenopausal females with hypertension were investigated. The nocturnal decline of systolic BP (SBP) was evaluated using 24-hour ambulatory BP monitoring (ABPM). A total of 163 postmenopausal females were eventually included in our study. The prevalence of reverse-dipper BP pattern was 32.3% in females with menopause age in their 40s and 40% in their 50s. However, after multivariate logistic regression analysis, menopause age was shown to be an independent risk factor for BP reverse dipping (Odds ratio [OR] 1.148; 95%CI 1.020 - 1.292; P = 0.020). Moreover, menopause age was negatively correlated with the decline rate of nocturnal SBP (r = -0.159; P < 0.05) and diastolic BP (r = -0.161; P < 0.05). Our study suggested that the menopause age might serve as a risk factor for reverse-dipper BP pattern in postmenopausal females with hypertension.

The identification of novel tumour-associated antigens is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we identified a membrane protein MMSA-1 (multiple myeloma special antigen-1) that was specifically expressed in MM and exhibited significantly positive correlation with MM. We then identified HLA-A*0201-restricted MMSA-1 epitopes and tested their cytotoxic T lymphocyte (CTL) response. The MMSA-1 epitope SLSLLTIYV vaccine was shown to induce an obvious CTL response in vitro. To improve the immunotherapy, we constructed a multi-epitope peptide vaccine by combining epitopes derived from MMSA-1 and Dickkopf-1 (DKK1). The effector T cells induced by multi-epitope peptide vaccine-loaded dendritic cells lysed U266 cells more effectively than MMSA-1/DKK1 single-epitope vaccine. In myeloma-bearing severe combined immunodeficient mice, the multi-epitope vaccine improved the survival rate significantly compared with single-epitope vaccine. Consistently, multi-epitope vaccine decreased the tumour volume greatly and alleviated bone destruction. The frequencies of CD4+ and CD8+ T cells was significantly increased in mouse blood induced by the multi-epitope vaccine, indicating that it inhibits myeloma growth by changing T cell subsets and alleviating immune paralysis. This study identified a novel peptide from MMSA-1 and the multi-epitope vaccine will be used to establish appropriate individualized therapy for MM.

The abnormalities of blood pressure (BP) nocturnal decline have been found to be predictive for carotid plaque and lacunar infarction in patients with hypertension. In this study, BP dipping patterns in postmenopausal females with hypertension was investigated. The nocturnal decline of systolic BP

OBJECTIVES:The aim of this study was to investigate the relationship between 24 h variation of blood pressure (BP) and carotid plaque in essential hypertensive patients with normal BP under anti-hypertensive treatment. PARTICIPANTS AND METHODS:A total of 322 hypertensive patients with systolic BP (SBP) and diastolic BP (DBP) within the normal range after routine treatment were continuously recruited and evaluated by ambulatory BP monitoring from 1 January 2014 to 31 July 2015. The exclusion criteria included participants younger than 18 or older than 90 years of age, pregnancy, night-work employment, and suffering from secondary hypertension. The prevalence of carotid plaque between different circadian BP pattern groups was analyzed using a χ-test. Logistic regression was applied to analyze the relationship between carotid plaque and ambulatory BP monitoring variables. RESULTS:All the individuals were divided into a 'carotid plaque' group (n=197) and a 'non-plaque' group (n=125) on the basis of whether the thickness of each plaque was at least 0.5 mm under the carotid ultrasound. In addition, patients were grouped into a dipper (10-20% nocturnal fall of BP in SBP) group and a nondipper (<10% nocturnal fall of BP in SBP) group on the basis of individual SBP variation. In the nondipper group, the number of patients with carotid plaque was higher than the patients without plaque (P=0.017). Logistic analysis showed that the nondipper pattern of BP was significantly associated with the formation of carotid plaque (odds ratio=1.731, P=0.041). CONCLUSION:A nondipper pattern of BP may serve as a risk factor for carotid plaque in treated hypertensive individuals with normal BP.

Grading of essential hypertension according to blood pressure (BP) level may not adequately reflect clinical heterogeneity of hypertensive patients. This study was carried out to explore clinical phenotypes in essential hypertensive patients using cluster analysis. This study recruited 513 hypertensive patients and evaluated BP variations with ambulatory blood pressure monitoring. Four distinct hypertension groups were identified using cluster analysis: (1) younger male smokers with relatively high BP had the most severe carotid plaque thickness but no coronary artery disease (CAD); (2) older women with relatively low diastolic BP had more diabetes; (3) non-smokers with a low systolic BP level had neither diabetes nor CAD; (4) hypertensive patients with BP reverse dipping were most likely to have CAD but had least severe carotid plaque thickness. In binary logistic analysis, reverse dipping was significantly associated with prevalence of CAD. Cluster analysis was shown to be a feasible approach for investigating the heterogeneity of essential hypertension in clinical studies. BP reverse dipping might be valuable for prediction of CAD in hypertensive patients when compared with carotid plaque thickness. However, large-scale prospective trials with more information of plaque morphology are necessary to further compare the predicative power between BP dipping pattern and carotid plaque.

Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

Recent studies suggested that nocturnal variations of blood pressure (BP) were closely related to type 2 diabetes. However, little information has been revealed about the relationship between reverse-dipper pattern of BP and type 2 diabetes. In this cross-sectional study, BP variations of 531 hypertensive patients were evaluated with ambulatory BP monitoring (ABPM). Diagnosis of diabetes in Chinese adults was made according to diabetes diagnostic criteria of 2015. Multivariate logistic regression was used to examine the relationships between type 2 diabetes and ABPM results. In the study, patients with reverse-dipper pattern (32.3%) had the highest prevalence of type 2 diabetes compared with dippers (21.4%) and nondippers (23.3%). After multivariate logistic regression, reverse-dipper BP pattern (OR 2.067, P = 0.024) and nondipper BP pattern (OR 1.637, P = 0.039) were found to be correlated with type 2 diabetes compared with dipper pattern. The results of our study also suggested that type 2 diabetes might contribute to the reverse-dipper pattern of BP (OR 1.691, P = 0.023). In addition, fasting glucose was negatively correlated with the decline rate of nocturnal SBP (r = -0.095, P = 0.029). Reverse-dipper pattern of BP in ABPM may be independently associated with type 2 diabetes in patients with hypertension.

Objective To investigate the relationship between the level of serum cystatin C (s-CC) and reverse-dipper blood pressure (BP) pattern. Design Cross-sectional study. Setting Single centre. Participants A total of 718 hypertensive patients were eventually recruited from cardiac clinics between 2012 and 2014 in the Second Affiliated Hospital, Xi'an Jiaotong University. They were diagnosed as essential hypertension according to their casual office records of systolic blood pressure (SBP) and/or diastolic blood pressure (DBP). Patients were excluded if they were <18 or >90 years old, under antihypertensive treatment, night workers, suffering from acute stroke or myocardial infarction within the past 6 months, diagnosed as secondary hypertension, sleep apnoea or other sleep disorders, renal failure, cardiac failure, chronic obstructive pulmonary disease, women during pregnancy or intolerant to the ambulatory BP monitoring (ABPM). Measurement The selected patients were evaluated with 24 hours ABPM. Peripheral venous blood samples were collected to evaluate the s-CC levels by ELISA. Methods The distribution of hypertensive patients with different levels of s-CC among each circadian BP pattern group was analysed using analysis of variance. Multinomial logistic regression analysis was applied to explore the relationship between the relevant variables and ABPM results. Results S-CC level in reverse-dipper group (1.19±0.53 mg/L) was increased significantly when compared with dipper group (1.06±0.36 mg/L) (p=0.021). In addition, after multinomial logistic regression analysis, s-CC (OR 1.717; 95% CI 1.033 to 2.854; p=0.037) and diabetes (OR 2.313; 95% CI 1.401 to 3.821; p=0.01) were significantly different between the reverse-dipper group and dipper group. On the other hand, the decline rate of nocturnal SBP (r=−0.117; p=0.002) and DBP (r=−0.089; p=0.018) was negatively correlated with the s-CC level. Conclusions The s-CC level was significantly higher in the reverse-dipper group than the dipper group and that s-CC was associated with the reverse-dipper pattern of BP examined with 24 hour ABPM.

Objective To investigate whether red blood cell distribution width (RDW) is associated with the blood pressure (BP) reverse-dipper pattern in patients with hypertension. Design Cross-sectional study. Setting Single centre. Participants Patients with essential hypertension were included in our study (n=708). The exclusion criteria included age <18 or >90 years, incomplete clinical data, night workers, diagnosis of secondary hypertension, under antihypertensive treatment, intolerance for the 24 h ambulatory BP monitoring (ABPM) and BP reading success rate <70%. Measurement Physical examination and ABPM were performed for all patients in our study. The value of RDW was measured using an automated haematology analyser. Statistical methods The distribution of RDW in patients with hypertension among different circadian BP pattern groups was analyzed using analysis of variance (ANOVA). Multinomial logistic regression was applied to explore the associations of RDW and other relevant variables with ABPM results. Results There was significantly increased RDW in reverse dippers (13.52±1.05) than dippers (13.25±0.85) of hypertension (p=0.012). Moreover, multinomial logistic regression analysis showed that RDW (OR 1.325, 95% CI 1.037 to 1.692, p=0.024) and diabetes mellitus (OR 2.286, 95% CI 1.380 to 3.788, p=0.001) were significantly different when comparing the reverse-dipper BP pattern with the dipper pattern. However, there was no difference of RDW between the non-dipper pattern and the reverse-dipper pattern (OR 1.036, 95% CI 0.867 to 1.238, p=0.693). In addition to this, RDW was negatively correlated with the decline rate of nocturnal systolic BP (r=−0.113; p=0.003) and diastolic BP (r=−0.101; p=0.007). Conclusions Our results suggested that RDW might associate with the abnormal dipper BP patterns of either reverse dipping or non-dipping homogeneously examined with 24 h ABPM.

ObjectiveTo investigate the associations of the blood pressure (BP) dipping status with carotid plaque in senior essential hypertensive patients of different sexes.Participants and methodsA total of 512 patients (275 men and 237 women) with essential hypertension who underwent ambulatory BP monitoring and carotid ultrasound assessment were recruited in our study. Binary logistic regression was used to analyze the associations of multiple risk factors with carotid plaque.ResultsAbnormal dipping [odds ratio (OR)=2.138, 95% confidence interval (CI) 1.170-3.908, P<0.05] and circadian decline rate of systolic BP (SBP) (OR=0.925, 95% CI 0.884-0.968, P<0.01) were found to be associated with carotid plaque in men. The level of night-time SBP (OR=1.022, 95% CI 1.003-1.042, P<0.05) and carotid plaque were associated with each other in women. In addition, as for all the patients in our study, abnormal dipping (OR=1.743, 95% CI 1.114-2.725, P<0.05), circadian decline rate of SBP (OR=0.950, 95% CI 0.922-0.980, P<0.01), the level of night-time SBP (OR=1.030, 95% CI 1.014-1.047, P<0.001), and the level of daytime diastolic BP (OR=0.971, 95% CI 0.946-0.998, P<0.05) were associated with carotid plaque, respectively.ConclusionOur results suggested that the abnormal dipping status of BP and circadian decline rate of SBP might serve as independent risk factors for carotid plaque, respectively, in men, as does night-time SBP in women. Therefore, personalized BP management may be necessary for hypertensive patients.

Intra-aortic balloon pump (IABP) has been extensively used in clinical practice as a circulatory-assist device. However, current literature demonstrated significantly varied indications for IABP application and prognosis.The objective of the study was to assess the potential benefits or risks of IABP treatment for acute myocardial infarction (AMI) complicated with or without cardiogenic shock.MEDLINE and EMBASE database were systematically searched until November 2014, using the terms as follows: IABP, IABC (intra-aortic balloon counterpulsation), AMI, heart infarction, coronary artery disease, ischemic heart disease, and acute coronary syndrome. Only randomized controlled trials (RCTs) that compared the use of IABP or non-IABP support in AMI with or without cardiogenic shock were included. Two researchers performed data extraction independently, and at the mean time, the risk of bias among those RCTs was also assessed.Of 3026 citations, 17 studies (n = 3226) met the inclusion criteria. There is no significant difference between IABP group and control group on the short-term mortality (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77-1.06; P = 0.214) and long-term mortality (RR, 0.91; 95% CI, 0.79-1.04; P = 0.155) in AMI patients with or without cardiogenic shock. These results were consistent when the analysis was performed on studies that only included patients with cardiogenic shock, both on short-term mortality (RR, 0.91; 95% CI, 0.77-1.08; P = 0.293) and long-term mortality (RR, 0.95; 95% CI, 0.83-1.10; P = 0.492). Similar result was also observed in AMI patients without cardiogenic shock. Furthermore, the risks of hemorrhage (RR, 1.49; 95% CI, 1.09-2.04; P = 0.013) and recurrent ischemia (RR 0.54, 95% CI 0.37 to 0.79; P = 0.002) were significantly higher in IABP group compared with control group.We did not observe substantial benefit from IABP application in reducing the short-and long-term mortality, while it might promote the risks of hemorrhage and recurrent ischemia. Therefore, IABP may be not an optimal therapy in AMI with or without cardiogenic shock until more elaborate classification is used for selecting appropriate patients.

Multiple myeloma-associated antigen-1 (MMSA-1) is a novel multiple myeloma (MM)-associated antigen which has been recently identified. Herein, we have tried to examine its clinical significance by studying the relationship between its expression and selected clinicopathological features. We extracted mononuclear cells from the bone marrow of MM patients and healthy donors and compared the MMSA-1 expression by RT-PCR and Western blot analysis. In addition, we also analyzed MMSA-1 expression in patients that were grouped based on selected clinical parameters. Moreover, the impact of MMSA-1 on patients' survival was also explored. MMSA-1 mRNA and protein were significantly upregulated in MM patients in comparison with healthy donors. Moreover, among the newly diagnosed and relapsed/refractory patients, the MMSA-1 expression was higher in relapsed/refractory patients. In addition, MMSA-1 mRNA expression not only showed significantly higher correlation with clinical parameters such as age, Durie and Salmon stage, bone lesion condition, albumin, creatinine and lactate dehydrogenase but also has a close relationship with myeloma bone disease-related cytokines, genetic abnormalities and treatment response. Multivariate COX analysis predicted MMSA-1 and LDH levels to be independently associated with a poor progression-free survival and overall survival in myeloma patients. Our findings provide initial proof of concept that MMSA-1 is a potent gene that is specifically expressed in MM patients and could be a feasible biomarker and independent prognostic factor.