Constructing an immune-related prognostic signature for predicting prognosis and immune response in hepatocellular carcinoma.

Background: Currently, there are few studies on immune-related prognostic analysis of hepatocellular carcinoma (HCC). Our aim was to establish an immune-correlated prognostic model for HCC. Methods: Immune-associated cells were obtained from the scRNA-seq dataset (GSE149614) of HCC. Differentially expressed genes between normal and tumor cells from immune-associated cells and the immune-related genes from the ImmPort database were used to identify immune-related differentially expressed genes (IRDEGs). Subsequently, the risk model was established in the TCGA-LIHC cohort (n = 438) from the Cancer Genome Atlas (TCGA) database by using Kaplan-Meier (K-M) survival curve, univariate/multivariate Cox regression analysis. Subsequently, we further analyzed tumor immune microenvironment characteristics, somatic mutation, immune checkpoint and its ligand expression levels between high- and low-risk groups, as well as drug sensitivity prediction. ICGC cohort was set as the validation cohort. TCGA-LIHC cohort and three independent the Gene Expression Omnibus (GEO) datasets (GSE54236, GSE14520, and GSE64041) was used to verify IRDEGs expression, as well as PCR assays using clinical samples. Results: The IRDEGs was composed of 4 genes, namely B2M, SPP1, PPIA, and HRG. The 438 HCC patients were divided into high- and low-risk group. The high-risk group was associated with poor prognosis, including higher T stage, advanced pathological stages, less immune cell infiltration, higher TP53 mutation rate, the high expression of CTLA4 and HAVCR2. Besides, high-risk populations benefit from most chemotherapy drugs. Similarly, the performance of the risk model was validated in the ICGC. All four datasets (TCGA-LIHC cohort, GSE54236, GSE14520, and GSE64041) and clinical q-PCR results demonstrated that, compared with normal samples, the expressions of B2M and HRG were lower in tumor samples, and the expression of SPP1 was higher. Conclusion: In summary, the immune-related prognostic signature had a good predictive performance on prognosis and immunotherapy for HCC patients.

The inverted U-shaped association between blood fibrinogen and rehospitalization risk in patients with heart failure.

Fibrinogen, a biomarker of thrombosis and inflammation, is related to a high risk for cardiovascular diseases. However, studies on the prognostic value of blood fibrinogen concentrations for heart failure (HF) patients are few and controversial. We performed a retrospective analysis among acute or deteriorating chronic HF patients admitted to a hospital in Sichuan, China, between 2016 and 2019, integrating electronic health care records and external outcome data (N = 1532). During 6 months of follow-up, 579 HF patients were readmitted within 6 months, and 46 of them died. Surprisingly, we found an inverted U-shaped association of blood fibrinogen levels with risk of readmission within 6 months but not with risk of death within 6 months. It was found that HF patients had the highest risk for readmission within 6 months after reaching the turning point for blood fibrinogen (2.4 g/L). In HF patients with low fibrinogen levels < 2.4 g/L, elevated fibrinogen concentrations were still significantly associated with a higher risk for readmission within 6 months [OR = 2.3, 95% CI (1.2, 4.6); P = 0.014] after controlling for relevant covariates. There was no significant association between blood fibrinogen and readmission within 6 months [(OR = 1.0, 95% CI (0.9, 1.1); P = 0.675] in HF patients with high fibrinogen (> 2.4 g/L). The effect difference for the two subgroups was significant (P = 0.014). However, we did not observe any association between blood fibrinogen and death within 6 months stratified by the turning point, and the effect difference for the stratification was not significant (P = 0.380). We observed an inverted U-shaped association between blood fibrinogen and rehospitalization risk in HF patients for the first time. Additionally, our results did not support that elevated blood fibrinogen was related to increased death risk after discharge.

Elevated blood malondialdehyde level contributed to a high stroke risk in a Chinese elderly population from rural areas: a cross-sectional study.

Individuals living in rural areas have a higher incidence rate of stroke than their urban counterparts in China. However, few studies have investigated the association between blood malondialdehyde (MDA), an end product of lipid oxidation caused by reactive oxygen species (ROS), and stroke risk in rural populations. We aimed to investigate whether blood MDA levels contribute to a higher stroke risk in a Chinese elderly population from rural areas. Data from 2011 to 2012 from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national cohort of older adults in China, were analyzed. Smooth curve and multivariable correction analyses were used to evaluate the association between blood MDA levels and stroke risk in elderly populations from rural and urban areas, respectively. The median age of all included participants (N = 1598) was 84.04 years. The results of the smooth curve model revealed a gradual upward trend in the association of blood MDA levels with stroke risk in rural participants but not in urban participants. Similarly, the conditional logistic regression analysis suggested a significant association between MDA levels and stroke risk in rural participants but not in urban participants after adjustments for related confounding factors (age, sex, current smoker, current drinker, regular exercise, BMI and cardiovascular diseases (hypertension, heart disease, atrial fibrillation and diabetes)) were made. In brief, among the elderly population in China, elevated blood MDA levels were associated with increased stroke risk in rural participants but not in urban participants.

Increased Global PSQI Score Is Associated with Depressive Symptoms in an Adult Population from the United States.

BACKGROUND: Although sleep problems are associated with a wide range of mental problems, it remains uncertain whether the global Pittsburgh Sleep Quality Index (PSQI) score is related to depressive symptoms in an adult population. PATIENTS AND METHODS: Data from the Midlife in the United States (MIDUS) study, including a general adult population, were obtained. A total of 1002 individuals (aged 34-84 years) were included in this study. Linear regression and logistic regression analyses were performed to investigate the association between sleep parameters from the PSQI score and depressive symptoms. RESULTS: The median age of all participants was 53.0 years old, and 45.2% of them were male. After adjustments were made for sociodemographic characteristics, lifestyle factors, currently diagnosed diseases and inflammatory markers, global PSQI score was significantly associated with depression score in the linear regression model (0.298 [0.207-0.389], P<0.001; Model 3). A higher global PSQI score was independently and significantly associated with depressive symptoms (score ≥16) in the logistic regression model (1.235 [1.150-1.325], P<0.001; Model 3). Stratified analysis showed that the independent association between global PSQI score and depressive symptoms was affected by hypnotics use, but not antidepressants use. CONCLUSIONS: A higher global PSQI score is significantly associated with a higher risk of depressive symptoms in an adult population from the United States. Future longitudinal and interventional studies are warranted to assess whether reducing the global PSQI score may improve symptoms of depression.

Sex differences in the associations between blood pressure and anxiety and depression scores in a middle-aged and elderly population: The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Anxiety and depression are considered risk factors for cardiovascular diseases (CVDs), but their relationship to blood pressure (BP) is still uncertain. Lifestyle factors and age-related comorbidities may confound these relationships. Our study aimed to evaluate the associations between BP and anxiety and depression scores in a population aged ≥49 years. METHODS: Data on 8504 participants from The Irish Longitudinal Study on Ageing (TILDA) were analyzed for associations between BP and anxiety and depression questionnaire scores, accounting for relevant confounding factors. RESULTS: Multivariable analyses showed negative associations between systolic BP and anxiety and depression scores, independent of age, body mass index (BMI), marital status, education level, smoking status, alcohol consumption, level of physical activity, self-reported CVDs (≥2) and antihypertensive medication use in men (coefficient=-0.112, P=0.013; coefficient=-0.051, P=0.026) but not in women (coefficient=-0.001, P=0.855; coefficient=-0.005, P=0.556). Diastolic BP was not associated with anxiety or depression scores in either men (coefficient=-0.018, P=0.223; coefficient=-0.001, P=0.924) or women (coefficient=-0.007, P=0.338; coefficient=-0.015, P=0.293) after adjusting for these same confounding factors. After a follow-up of 4 years, lower BP in subjects not using antihypertensive medications was significantly associated with more anxiety and depression events. LIMITATION: Time-varying confounding factors may have interfered with our results. CONCLUSION: Our results show that systolic BP in a middle-aged and elderly population is negatively associated with anxiety and depression scores in men but not women after adjustment for a range of lifestyle factors. These results contrast with the predisposition of anxious or depressed participants to CVDs in later life when decades of unhealthy lifestyles have persisted.

The Association between Serum Retinol-Binding Protein 4 Levels and Cardiovascular Events in Patients with Chronic Kidney Disease.

OBJECTIVE: The study aimed to assess whether serum retinol-binding protein 4 (RBP4) is associated with a risk of cardiovascular (CV) events in chronic kidney disease (CKD) patients. METHODS: One hundred sixty-nine patients with CKD were followed for a mean of 36 months (range, 5-39 months). Serum RBP4 and other laboratory indicators were measured at baseline. The relationship between RBP4 and the risk of CV events was evaluated by using Cox regression analysis. RESULTS: Patients with higher serum RBP4 levels had a higher rate of CV events and a higher mortality in a univariate analysis (P < 0.001). The multivariate Cox proportional hazard analysis revealed that RBP4 (hazard ratio, 2.259; 95% confidence interval, 2.067-5.489; P = 0.002) is an independent prognostic factor for CV events in patients with CKD. Kaplan-Meier analysis demonstrated that patients with RBP4 above the median value (>33.86 mg/L) had a higher rate of CV events than did patients with RBP4 at or below the median value (≤33.86 mg/L; P < 0.001). CONCLUSION: RBP4 levels are associated with CV events in patients with CKD. Elevated serum RBP4 levels may indicate an increased risk of CV complications in CKD patients.

The Relationship Between Global Sleep Score And Inflammatory Markers In Obese Adults From The United States.

BACKGROUND: Poor sleep is a risk factor for cardiovascular diseases (CVDs). The underlying pathogenesis is not clear. Levels of inflammatory markers, such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-ɑ (TNF-ɑ), have been found to be elevated in patients with CVDs. AIM: The study aimed to investigate the associations between sleep quality and serum inflammatory markers in a cohort of obese adults. METHODS: This was a second analysis of the data from the Midlife in the United States (MIDUS) study, a longitudinal study of a national (US) sample of adults. A total of 1255 participants completed comprehensive biological assessments. The associations between global sleep score and serum levels of inflammatory markers were analyzed. RESULTS: Univariate analysis showed that a higher global sleep score was correlated with lower age (r = -0.079, P= 0.009), higher BMI (r = 0.100, P= 0.001) and heavier perceived stress (r = 0.335, P<0.001). Multivariate linear regression analysis showed that the global sleep score was positively related to levels of IL-6 (Sß=0.074, P=0.009), IL-8 (Sß=0.089, P=0.002), TNF-ɑ (Sß=0.0.082, P=0.005), E-selectin (Sß=0.071, P=0.016) and intercellular adhesion molecule-1 (ICAM-1, Sß=0.117, P<0.001) after adjustments were made for age, gender, race, marital status, education, current smoking status, physician-diagnosed CVDs and respiratory diseases, BMI and perceived stress. However, the global sleep score was not associated with serum IL-10 (Sß=-0.021, P=0.463) and CRP (Sß=0.035, P=0.059) levels after adjustments were made for these confounding factors. CONCLUSION: Poor sleep is positively associated with serum inflammatory marker levels among obese adults. Sufficient sleep may be particularly important for obese adults to prevent CVDs.

Lithium chloride (LiCl) induced autophagy and downregulated expression of transforming growth factor ß-induced protein (TGFBI) in granular corneal dystrophy.

This study evaluated whether lithium chloride (LiCl) prevents cytoplasmic accumulation of mutant-transforming growth factor ß-induced protein (Mut-TGFBI) in granular corneal dystrophy (GCD) via activation of the autophagy pathway. Levels of TGFBI and microtubule-associated protein 1A/1B-light chain 3 (LC3) in 3 GCD patients and healthy controls were analyzed by immunohistochemistry (IHC) staining and Western blot. Primary corneal fibroblasts were isolated and transfected with wild type or mutant type TGFBI over-expressed vectors, and then treated with LiCl and/or autophagy inhibitor 3-methyladenine (3-MA). Then, levels of TGFBI, glycogen synthase kinase-3 (GSK-3) and LC3-I/-II were detected. Cell viability and transmission electron microscopy assay were also performed. Levels of TGFBI and LC3 were significantly increased in GCD patients. Over-expression of mutant type TGFBI inhibited cell viability and induced autophagy in corneal fibroblasts. LiCl downregulated the expression of TGFBI in mutant type TGFBI over-expressed cells in a dose- and time-dependent manner. LiCl enhanced autophagy in mutant type TGFBI over-expressed cells and recovered cell viability in those cells. However, the effects of LiCl were partly attenuated when autophagy was suppressed by 3-MA. To summarize, treatment with LiCl inhibited the expression of TGFBI and recovery the inhibitory of mutant type TGFBI in cell viability, at least part through enhancing of autophagy. These data strongly suggest that LiCl may be useful in the treatment of GCD.

Genome-wide identification, evolution and expression analysis of RING finger protein genes in Brassica rapa.

More and more RING finger genes were found to be implicated in various important biological processes. In the present study, a total of 731 RING domains in 715 predicted proteins were identified in Brassica rapa genome (AA, 2n = 20), which were further divided into eight types: RING-H2 (371), RING-HCa (215), RING-HCb (47), RING-v (44), RING-C2 (38), RING-D (10), RING-S/T (5) and RING-G (1). The 715 RING finger proteins were further classified into 51 groups according to the presence of additional domains. 700 RING finger protein genes were mapped to the 10 chromosomes of B. rapa with a range of 47 to 111 genes for each chromosome. 667 RING finger protein genes were expressed in at least one of the six tissues examined, indicating their involvement in various physiological and developmental processes in B. rapa. Hierarchical clustering analysis of RNA-seq data divided them into seven major groups, one of which includes 231 members preferentially expressed in leaf, and constitutes then a panel of gene candidates for studying the genetic and molecular mechanisms of leafy head traits in Brassica crops. Our results lay the foundation for further studies on the classification, evolution and putative functions of RING finger protein genes in Brassica species.

DPPH·-luminol chemiluminescence system and its application in the determination of scutellarin in pharmaceutical injections and rat plasma with flow injection analysis.

In this article, a DPPH·-luminol chemiluminescence (CL) system was reported and the CL mechanism was discussed according to the CL kinetic properties after sequence injecting DPPH· into the DPPH·-luminol reaction mixture. It was observed that scutellarin could inhibit the CL response of the DPPH·-luminol system. Based on this observation, a simple and rapid flow injection CL method was developed for the determination of scutellarin using the inhibition effect in alkaline medium. The optimized chemical conditions for the CL reaction were 5 × 10-6  mol/L DPPH· and 1.0 × 10-4  mol/L luminol in 0.01 mol/L NaOH. Under optimized conditions, the CL intensity was inversely proportional to the concentration of scutellarin over the ranges 5-2000 and 40-3200 ng/ml in pharmaceutical injection and rat plasma, respectively. The limits of detection (S/N = 3) were 5 and 40 ng/ml in preparations and rat plasma, respectively. Furthermore, the precision, recovery and stability of the validated method were acceptable for the determination of scutellarin in both pharmaceutical injections and rat plasma. The presented method was successfully applied in the determination of scutellarin in pharmaceutical injections and real rat plasma samples.

Crystal structure of azilsartan methyl ester ethyl acetate hemisolvate.

The title compound, C26H22N4O5 (systematic name: methyl 2-eth-oxy-1-{4-[2-(5-oxo-4,5-di-hydro-1,2,4-oxa-diazol-3-yl)phenyl]benz-yl}-1H-1,3-benzo-diazole-7-carboxyl-ate ethyl acetate hemisolvate), was obtained via cyclization of methyl (Z)-2-eth-oxy-1-{(2'-(N'-hy-droxy-carbamimido-yl)-[1,1'-biphen-yl]-4-yl)meth-yl}-1H-benzo[d]imidazole-7-carboxyl-ate with diphen-yl carbonate. There are two independent mol-ecules (A and B) with different conformations and an ethyl acetate solvent mol-ecule in the asymmetric unit. In mol-ecule A, the dihedral angle between the benzene ring and its attached oxa-diazole ring is 59.36 (17); the dihedral angle between the benzene rings is 43.89 (15) and that between the benzene ring and its attached imidazole ring system is 80.06 (11)°. The corres-ponding dihedral angles in mol-ecule B are 58.45 (18), 50.73 (16) and 85.37 (10)°, respectively. The C-O-C-Cm (m = meth-yl) torsion angles for the eth-oxy side chains attached to the imidazole rings in mol-ecules A and B are 93.9 (3) and -174.6 (3)°, respectively. In the crystal, the components are linked by N-H⋯N and C-H⋯O hydrogen bonds, generating a three-dimensional network. Aromatic π-π stacking inter-actions [shortest centroid-centroid separation = 3.536 (3)Å] are also observed.

Shp2 regulates chlorogenic acid-induced proliferation and adipogenic differentiation of bone marrow-derived mesenchymal stem cells in adipogenesis.

Chlorogenic acid (CGA) exhibits various biological properties, including the inhibition of oxidation, obesity, apoptosis and tumorigenesis. CGA is also able to promote cell survival and proliferation. The aim of the present study was to determine the effects and underlying molecular mechanisms of CGA on the adipogenesis of bone marrow­derived mesenchymal stem cells (BMSCs). Treatment with CGA had a marginal effect on cell proliferation, by promoting the expression levels of phosphorylated Akt and cyclin D1. Furthermore, treatment with CGA also upregulated the phosphorylation of extracellular signal­regulated kinase (Erk) and inhibited the adipocyte differentiation of BMSCs by inhibiting the expression of peroxisome proliferator­activated receptor (PPAR)γ and CCAAT/enhancer binding protein (C/EBP)α. However, knockdown of the expression of Shp2 attenuated CGA­induced proliferation and inhibited the phosphorylation of Akt and expression of cyclin D1. Furthermore, CGA treatment upregulated Erk phosphorylation and decreased the expression levels of PPARγ and CEBPα, which was inhibited by treatment with the Shp2 PTPase activity inhibitor, NSC­87877. The results of the present study suggested that CGA­induced Akt and Erk pathways regulate proliferation and differentiation and that Shp2 is important in the proliferation and differentiation of BMSCs.

[Comparative observation on efficacy of jieyu pill and maprotiline in treating depression].

OBJECTIVE: To investigate the clinical efficacy, adverse reaction and safety of Jieyu pill (JYP) in treating depression. METHODS: The randomized controlled trial was conducted in 28 patients in the treated group and 29 patients in the control group treated with maprotiline (Map). The efficacy of treatment was evaluated before treatment and 14, 28 and 42 days after treatment, with Hamilton depression rating scale (HAMD), self-rating scale for depression (SDS), self-rating scale for anxiety (SAS) and clinical global impression (CGI), the adverse reaction was assessed by Asberg Rating Scale (ARS). RESULTS: JYP was effective in treating depression, the markedly effective rate being 78.8%, corresponded to that of Map (82.8%, P > 0.05). After treatment, the scores assessed by HAMD, SDS and SAS were all lower than those before treatment (P < 0.01) respectively, but comparison between the two groups showed insignificant difference (P > 0.05). However, scores of ARS were significantly lower in the treated group than that in the control group, and the efficacy index of JYP was significantly higher than that of Map (P < 0.01). CONCLUSION: JYP in treating depression shows the efficacy corresponded to that of Map and with less adverse reaction.