[Pathological study on the relationship between nucleic acid oxidative stress and heart failure with preserved ejection fraction in patients aged over 85 years].

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.

Causal roles of daytime sleepiness in cardiometabolic diseases and osteoporosis.

OBJECTIVE: Daytime sleepiness has some association with cardiometabolic diseases and osteoporosis, but it is unknown whether their relationship is causal. This two-sample Mendelian randomization (MR) study aims to explore their causal relationship. MATERIALS AND METHODS: We included the largest genome-wide association studies (GWASs) associated with daytime sleepiness, cardiometabolic diseases and osteoporosis. 34 single nucleotide polymorphisms (SNPs) were used as the instrumental variables of daytime sleepiness. RESULTS: Genetic predisposition to excessive daytime sleepiness was strongly associated with increased risk of coronary artery disease (beta-estimate: 0.610, 95% confidence interval [CI]: 0.128 to 1.093, standard error [SE]: 0.246, p-value=0.013) and may increase the incidence of type 2 diabetes (beta-estimate: 0.614, 95% CI: 0.009 to 1.219, SE: 0.309, p-value=0.047). We found no causal influence of daytime sleepiness on heart failure, atrial fibrillation, cerebral ischemia, intracerebral hemorrhage, forearm bone mineral density (FA-BMD), femoral neck BMD (FN-BMD), and lumbar spine BMD (LS-BMD). CONCLUSIONS: This study suggested that excessive daytime sleepiness was causally associated with increased risk of coronary artery disease, which may benefit to prevent this disease.

[Study on the clinical significance of miR-100 expression in the invasion and metastasis of hepatocellular carcinoma].

Objective: To study the miR-100 expression levels in the tissues of hepatocellular carcinoma patients, and to further explore the correlation between miR-100 and the invasion and metastasis of hepatocellular carcinoma cells and its effect on patients' prognostic survival. Methods: Clinicopathological data of 70 cases that underwent hepatectomy from December 2013 to December 2016 in the Department of Hepatobiliary and Pancreatic Surgery of Henan Provincial People's Hospital were retrospectively analyzed. Real-time fluorescent quantitative PCR was used to detect the different miR-100 expression levels in cancerous and adjacent tissues. The expression of miR-100 with different clinicopathological features was compared, and the prognostic factors of patients with hepatocellular carcinoma were comprehensively analyzed. The correlation between miR-100 and patients' clinicopathological features was tested by χ(2). Kaplan-Meier method was used to draw the survival curve. Log-rank test was used to examine the survival rate difference in each subgroup. Cox regression model was used to analyze the multivariate prognosis. Results: miR-100 expression was down-regulated to a different degree in hepatocellular carcinoma tissues than the corresponding adjacent tissues. Among them, the down-regulated expression of miR-100 in hepatocellular carcinoma tissues accounted for 82.9% (58/70, P < 0.05) of all cases when compared to corresponding paracancerous tissues. miR-100 expression level was significantly correlated to high Edmondson's grade, high TNM stage and intrahepatic metastasis (P < 0.05). The overall survival time of miR-100 positive expression was significantly higher than that of miR-100 negative expression (Log-rank χ(2) = 8.257, P < 0.05). Univariate survival analysis results revealed that the miR-100 expression level, tumor size, TNM stage, Edmondson's grade, and presence or absence of venous tumor thrombosis had a poor prognosis (P < 0.05). Cox multivariate regression analysis showed that the tumor size, Edmondson's grade, and miR-100 expression level were independent factors affecting the prognostic survival in hepatocellular carcinoma patients. In addition, patients with low positive expression rate of miR-100, large tumors and high Edmondson's grade had a poor prognosis. Conclusion: The level of miR-100 expression in hepatocellular carcinoma cells is low, so it is closely related to the invasion and metastasis and affects the prognostic survival of hepatocellular carcinoma patients.

[The effect of estrogen level on Budd Chiari syndrome related hepatocellular carcinoma].

Objective: To investigate the effect of estrogen level on Budd Chiari syndrome related hepatocellular carcinoma. Methods: Immunohistochemical method was used to detect estrogen receptor-α and estrogen receptor-ß expression in 38 cases of Budd Chiari syndrome related hepatocellular carcinoma and 50 cases of HBV related hepatocellular carcinoma.Hepatoma cells of Budd Chiari syndrome related hepatocellular carcinoma were exposed to different concentrations of Estrogen for 48 hours. Tetrazolium bromide (MTT) colorimetry was used to analyze cell proliferation activities; cell cycle was analyzed by flow cytometry (FCM); cell apoptosis was analyzed by flow cytometry (FCM) and Casepase-3 activity was measured after induced by adriamycin(ADM). Results: The positive rate of estrogen receptor-α expression in the tissues of Budd Chiari syndrome related hepatocellular carcinoma was 71.05%, which was higher than that (32%)in HBV related hepatocellular carcinoma tissue evidently (P<0.01). The positive rate of estrogen receptor-ß expression in the tissues of Budd Chiari syndrome related hepatocellular carcinoma was 68.4%, which was higher than that (26%)in HBV related hepatocellular carcinoma tissue evidently (P<0.01). With the concentrations of estrogen increasing, MTT Assays showed that estrogen level increased the cell proliferation activities of Budd Chiari syndrome related hepatocellular carcinoma. The number of cells at stage S and G2/M were significantly increased and cells at stage G0/G1 were reduced with the increasing concentrations of estrogen. After being incubated under the different concentrations of estrogen for 48 h, the apoptosis rates decreased gradually and the Casepase-3 activity was significantly reduced with the increasing concentration of estrogen. Conclusions: Estrogenreceptor expression may have an important influence on hepatocellular carcinoma cell biology difference between Budd Chiari syndrome related hepatocellular carcinoma and HBV related hepatocellular carcinoma. Estrogen level can promote cell proliferation and cell cycle, and inhibit the apoptosis of hepatoma cells of Budd Chiari syndrome related hepatocellular carcinoma in vitro, and these effects were increased with the increasing of estrogen level.

[The prognostic value of circulating microRNA-29b in left ventricular hypertrophy in patients with hypertension].

Objective: To analyze the relationship between the level of microRNA-29b in circulation and left ventricular hypertrophy in hypertensive patients. Methods: A total of 240 subjects from Henan Province People's Hospital from June 2015 to June 2018 were included in the present study. Among them, 160 were hospitalized patients, and were divided into two groups. Patients with simple hypertension and had no left ventricular hypertrophy (80 cases) were in the simple hypertension group (HBP-NLVH), and patients with hypertension combined with left ventricular hypertrophy (80 cases) were in the high blood pressure with left ventricular hypertrophy group (HBP-LVH). Normal control subjects (80 cases) were those with no hypertension and randomly selected from the medical center of Henan Province People's Hospital. Serum microRNA-29b expressions were detected by real time fluorescence quantitative PCR. The thickness of interventricular septum (IVSD) and left ventricular posterior wall thickness (LVPWD) were measured by echocardiography. Results: Compared with the normal control group (1.95±0.79), the relative expression of microRNA-29b in the patients both in the HBP-NLVH group (2.67±0.92) and the HBP-LVH group (5.12±1.23) was up-regulated, and the difference between normal control and patients was statistically significant (P<0.05). In patients, the microRNA-29b level in the HBP-LVH group was significantly higher than that in the HBP-NLVH group (P<0.05). The expression level of microRNA-29b was positively correlated with IVSD (r=0.71, P<0.05) and LVPWD (r=0.74, P<0.05), respectively. The sensitivity and specificity of serum microRNA-29b levels in the diagnosis of left ventricular hypertrophy in hypertension patients were 96.8% and 91.3%, respectively. Conclusion: Serum microRNA-29b level is elevated in hypertensive patients with left ventricular hypertrophy, and is positively correlated with left ventricular hypertrophy. The circulation microRNA-29b might be a useful biomarker with prognostic value in left ventricular hypertrophy in hypertension patients.

[Value of RNA oxidation product 8-oxo-Gsn in evaluating renal function in patients with chronic kidney disease].

Objective: To investigate the relationship of DNA oxidative product 8-oxo-dGsn and RNA oxidative product 8-oxo-Gsn with chronic kidney disease (CKD). Methods: Between January 2015 and December 2016, 146 cases of CKD (30, 30, 31, 30 and 25 cases of CKD stage 1-5, respectively) were collected in the Department of Nephrology in Beijing Hospital. Among them, 70 cases were male, accounting for 47.95%. The age distribution ranged from 21 to 88 years, with an average age of (56.43±16.79) years. Their fasting blood and morning urine were collected. The levels of 8-oxo-dGsn and 8-oxo-Gsn in plasma and urine were quantified by isotope-diluted liquid chromatography mass spectrometry (MS)/MS (ID-LC-MS/MS). Results: The urine 8-oxo-Gsn/Cr in patients with CKD stage 1-5 was (3.07±1.07) µmol/mol, (3.42±1.34) µmol/mol, (3.72±1.47) µmol/mol, (3.90±1.93) µmol/mol and (3.75±2.26) µmol/mol, respectively. The urinary 8-oxo-Gsn content in CKD stage 4 patients was significantly higher than those of other 4 stages (P<0.05). The serum/urine ratio of 8-oxo-Gsn was 0.02±0.02, 0.03±0.02, 0.06±0.04, 0.10±0.05 and 0.34±0.03, respectively, and in CKD stage 4 and 5 patients, it increased significantly, especially in CKD stage 5 cases (P<0.05). Expression of 8-oxo-Gsn had a good correlation with renal function[the Spearman 's correlation coefficient: serum 8-oxo-Gsn and serum creatinine was 0.629 (P<0.001); urine/serum 8-oxo-Gsn and eGFR was 0.799 (P<0.001); serum/urine 8-oxo-Gsn and serum/urine creatinine was 0.888 (P<0.001)]. With age increasing, CKD patients showed increased RNA oxidation, and 8-oxo-Gsn increased significantly in patients over 60 years (P<0.05). After multiple linear regression analysis, 8-oxo-Gsn was only associated with serum creatinine (ß=0.656, t=8.275, P<0.001). Conclusions: Our finding indicates that the RNA oxidation occurs in patients with renal disease, and its oxidation increased as the disease progressing. The significant increase in the ratio of plasma and urinary 8-oxo-Gsn is of great importance on evaluating renal function.

Characterization of the novel HLA-B*40:366 allele by sequencing-based typing.

HLA-B*40:366 differs from HLA-B*40:06:01:01 by one nucleotide substitution at position 362.

Characterization of the novel HLA-C*07:613 allele by sequencing-based typing.

HLA-C*07:613 differs from HLA-C*07:01:01:01 by one nucleotide substitution at position 454.

Characterization of the novel HLA-C*03:02:17 allele by sequencing-based typing.

HLA-C*03:02:17 differs from HLA-C*03:02:02:01 by one nucleotide substitution at position 393.

Characterization of the novel HLA-B*40:01:51 allele by sequencing-based typing.

HLA-B*40:01:51 differs from HLA-B*40:01:01 by 2 nucleotide substitutions at position 72 and 126.

Characterization of the novel HLA-B*48:43 allele by sequencing-based typing.

HLA-B*48:43 differs from HLA-B*48:01:01:01 by two nucleotide substitutions at positions 981 and 986.

A novel HLA-DRB1*07 allele, HLA-DRB1*07:01:22, identified in a Chinese individual.

HLA-DRB1*07:01:22 differs from HLA-DRB1*07:01:01:01 at position 244 (C>T) in exon 2.

Characterization of the novel HLA-DQB1*05:155 allele by sequencing-based typing.

HLA-DQB1*05:155 differs from HLA-DQB1*05:01:01 by one nucleotide substitution at position 474 (G>C).

Characterization of the novel HLA-A*02:07:10 allele by sequencing-based typing.

HLA-A*02:07:10 differs from HLA-A*02:07:01 by one nucleotide substitution at position 117.

Characterization of the novel HLA-DRB1*13:241 allele by sequencing-based typing.

HLA-DRB1*13:241 differs from HLA-DRB1*13:02:01 by one nucleotide substitution at position 335.

Characterization of a novel HLA-C*04 allele, HLA-C*04:277.

HLA-C*04:277 has one nucleotide difference from HLA-C*04:01:01:01 at position 1034 (G>A).

A new HLA-B*55 allele, B*55:83N with a stop codon in exon 4 generated by a point mutation, identified in a Chinese individual.

The new allele HLA-B*55:83N differs from HLA-B*55:02:01:01 by a single nucleotide.

Persistence of antibodies acquired by natural hepatitis E virus infection and effects of vaccination.

OBJECTIVE: Naturally acquired anti-hepatitis E virus (HEV) immunity can protect against new HEV infections. The aim of this study was to analyse the persistence of naturally acquired anti-HEV immunoglobulin (Ig) G and anti-HEV IgG concentrations after vaccination. METHODS: We examined the seropositivity rates of participants included in a phase 3 clinical efficacy trial (67 months' follow-up) for a HEV vaccine (Hecolin; Xiamen Innovax Biotech, China) and predicted long-term persistence using mixed-effect models. RESULTS: The analysis focused on 2242 baseline seropositive participants in a control group (placebo recipients) and 2031 baseline seropositive participants in an vaccine group (vaccine recipients) who received 1 to 3 doses of Hecolin. Naturally acquired anti-HEV IgG levels decreased steadily independent of the initial antibody level; 50% of the placebo recipients were expected to have undetectable antibody concentrations after 14.5 years. After immunization with Hecolin, the power-law model and the modified power-law model predicted that 82.1 and 99.4% of the participants, respectively, would remain seropositive for anti-HEV IgG for 30 years after vaccination. CONCLUSIONS: Whereas naturally acquired anti-HEV IgG levels decrease steadily, HEV vaccination induces long-lasting, high-level anti-HEV IgG concentrations.