Objective:To investigate the prognostic value of preoperative red blood cell distribution width (RDW) for hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 025 HCC patients who were admitted to three medical centers (586 in the First Affiliated Hospital of Xi'an Jiaotong University, 248 in the Second Affiliated Hospital of Xi'an Jiaotong University and 191 in the Qinghai University Affiliated Hospital) between April 2002 and August 2017 were collected. There were 809 males and 216 females, aged (54±11)years, with a range from 16 to 83 years. The average coefficient of variation of RDW (RDW-CV) of 1 025 patients was 14.3%. Of 1 025 patients, 347 cases had high RDW of RDW-CV >14.3%, and 678 had low RDW of RDW-CV ≤14.3%. Observation indicators: (1) clinico-pathological data of HCC patients; (2) influencing factors for prognosis of HCC patients; (3) follow-up and survival. (4) stratified analysis of independent influencing factors. Follow-up was performed by outpatient examination, telephone interview or internet interview to detect postoperative survival of patients up to October 2017. Measurment data with normal distribution were represented as Mean±SD, and measurment data with skewed distribution were described as M (range). Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. The Graphpad Prism 7.0 was used to draw survival curves, and Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the COX proportional hazard model. Results:(1) Clinicopathological data of HCC patients: cases with age ≤70 years or >70 years, cases without cirhhosis or with cirhhosis , cases of Child-Pugh grade A or Child-Pugh grade B or C, cases with the level of alpha fetoprotein (AFP) ≤200 μg/L or >200 μg/L, cases with single tumor or multiple tumors were 313, 34, 152, 186, 161, 53, 158, 143, 186, 109 for high RDW patients, versus 641, 37, 359, 310, 415, 48, 367, 227, 547, 131 for low RDW patients, respectively, showing significant differences in above indicators between the two groups ( χ2=6.709, 6.787, 23.906, 7.114, 34.375, P<0.05). (2) Influencing factors for prognosis of HCC patients: results of univariate analysis showed that age, Child-Pugh grade, AFP, RDW-CV, tumor diameter, the number of tumors were related factors for prognosis of patients ( hazard ratio=1.388, 1.432, 1.534, 1.455, 2.813, 1.505, 95% confidence interval as 1.004-1.920, 1.086-1.887, 1.263-1.864, 1.211-1.748, 2.293-3.450, 1.173-1.932, P<0.05 ). Results of multivariate analysis showed that age, RDW-CV, tumor diameter and the number of tumors were independent factors for prognosis of patients ( hazard ratio=1.020, 1.340, 2.427, 1.438, 95% confidence interval as 1.007-1.032, 1.027-1.749, 1.801-3.272, 1.057-1.956, P<0.05). (3) Follow-up and survival: 1 025 patients were followed up for 1-124 months, with a median follow-up time of 25 months. The median survival time was 23 months for high RDW patients, versus 44 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=11.640, P<0.05). (4) Stratified analysis of independent influencing factors: the results of stratified analysis of 3 independent influencing factors including age, tumor diameter and the number of tumors showed that in the 954 patients with age ≤70 years, the median survival time was 25 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=14.030, P<0.05). In the 71 patients with age >70 years, the median survival time was 11 months for high RDW patients, versus 29 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=0.933, P>0.05). In the 459 patients with tumor diameter ≤5 cm, the median survival time was 44 months for high RDW patients, versus 76 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=8.660, P<0.05). In the 487 patients with tumor diameter >5 cm, the median survival time was 14 months for high RDW patients, versus 18 months for low RDW patients, showing no significant difference in the overall survival between the two groups ( χ2=2.950, P>0.05). In the 733 patients with single tumor, the median survival time was 20 months for high RDW patients, versus 48 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=13.530, P<0.05). In the 240 patients with multiple tumors, the median survival time was 15 months for high RDW patients, versus 20 months for low RDW patients, showing a significant difference in the overall survival between the two groups ( χ2=6.820, P<0.05). Conclusions:Preoperative RDW can be used as a predictive index for prognosis of HCC patients, and patients with high RDW have poorer prognosis. RDW have better predictive value in patients with age ≤70 years or tumor diameter ≤5 cm.

Objective: To explore the association between hypothyroidism and sleep breathing disorders in patients with coronary heart disease (CHD). Methods: A total of 784 patients with CHD were consecutively enrolled at the Emergency & Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. According to thyroid function test results, patients were divided into hypothyroidism group (79 cases) and non-hypothyroidism group (705 cases). All patients had undergone sleep monitoring. The sleep apnea status was compared between the two groups. Multivariate logistic regression and linear regression models were used to analyze the association between hypothyroidism and sleep breathing disorders in patients with CHD. Results: The proportion of females, mean body weight and body mass index in the hypothyroidism group were higher than those in the non-hypothyroidism group [26.6% vs.16.2%, (78.6±11.6) kg vs. (75.7±12.0) kg, (27.7±3.2) kg/m² vs. (26.6±3.5) kg/m², all P<0.05]. Patients in hypothyroidism group had a decreased average oxygen saturation (SaO₂) compared with patients in non-hypothyroidism group [ (93.2±2.9) % vs. (93.9±2.0) %, P=0.030]. In addition, events of hypoventilation in hypothyroidism group were significantly higher than those in non-hypothyroidism group[92.5 (45.8, 758.3) times vs. 68.0 (33.0, 125.0) times, P=0.013]. There were no significant differences in apnea hypopnea index, diagnosis of obstructive sleep apnea and other sleep breathing parameters between the two groups (P>0.05). A multiple linear regression analysis found that in patients with CHD, the correlation between hypothyroidism and average sleep SaO₂ was significant (β=-0.508, 95%CI -0.989--0.026, P=0.039). Conclusions: CHD patients with hypothyroidism had a lower sleep average SaO₂, and a higher sleep hypopnea events. There is a correlation between hypothyroidism and sleep hypoxia in patients with CHD. Clinical trial registration clinicalTrials.gov, NCT03362385.

Objective: To investigate the impact of moderate/severe obstructive sleep apnea (OSA) on the prognosis of acute myocardial infarction. Methods: We prospectively selected patients with acute myocardial infarction (AMI) who were hospitalized at the Emergency Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. Patients who met the inclusion criteria were examined with portable sleep respiration monitoring. Patients were divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 beats/hour) and no/mild OSA group (AHI<15 beats/hour) according to sleep AHI. The incidence of major adverse cerebrovascular events (MACCE) after discharge was compared between the two groups, and the independent risk factors of MACCE were analyzed. Results: A total of 432 patients were enrolled in this study, including 211 moderate/severe OSA patients (48.8%). Compared with no/mild OSA group,patients with moderate/severe OSA had higher body mass index ((27.17±3.22) kg/m² vs. (25.55±3.44) kg/m², t=-5.033,P<0.001), higher proportion of history of percutaneous coronary intervention (PCI) (18.5%(39/211) vs. 8.6%(19/221), χ²=9.076,P=0.003), and higher proportion of 3-vessel disease (31.3%(66/211) vs. 24.9%(55/221), χ²=10.196,P=0.017). The median follow-up time was 1.0 (0.7, 1.7) years. The incidence of MACCE in the moderate/severe OSA and no/mild group was 19.9%(42/211) and 11.3%(25/221), respectively. Kaplan-Meier analysis showed a higher cumulative risk of MACCE in patients with moderate/severe OSA (log-rank test,χ²=5.467, P=0.019). Multivariate Cox regression analysis showed that moderate/severe OSA (HR=1.915, 95%CI 1.016-3.611, P=0.045) and diabetes mellitus (HR=1.819, 95%CI 1.022-3.238, P=0.042) were independent risk factors for MACCE at 1 year post discharge in patients with AMI. Conclusions: Nearly half of AMI patients are complicated with moderate/severe OSA in this patient cohort. Coronary artery disease is more severe in AMI patients complicating with moderate/severe OSA. Moderate/severe OSA is an independent risk factor for MACCE at 1 year after discharge in patients with AMI. Whether the prognosis of AMI can be improved by intervention of OSA remains to be investigated. Trial Registration Clinical Trial.gov, NCT03362385.

Objective To examine the prevalence of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS),and to evaluate the relationship of OSA with inflammatory biomarkers in ACS patients.Methods Patients with ACS treated at Beijing Anzhen Hopital from June 2015 to May 2017 were enrolled.Subjects were evaluated for OSA by sleep study,and were divided into a normal-mild OSA group (Apnea Hypopnea Index,AHI ＜ 15 times/h) and a moderate-severe OSA group (AHI ≥ 15 times/h).Laboratory examination and sleep study were monitored to analyze the effects of OSA on biomarkers by LSD-t test,Mann-whitney U test,or Chi-square test.Correlation analysis was performed to analyze the association of OSA with high sensitivity C-reactive protein (hs-CRP) by Spearman correlation anaylsis.Results A cohort of 836 patients with ACS were enrolled including 408 patients in the normal-mild OSA group and 428 patients in the moderate-severe OSA group.The levels of leukocyte(x 109L) [7.78 (6.33,9.86) vs 7.29 (6.01,9.16),P=0.006],neutrophils(× 109L) [5.05 (3.84,7.23)vs 4.80 (3.74,6.66),P=0.044],monocytes(x 109L) [0.42 (0.33,0.54) vs 0.39 (0.31,0.51),P=0.033],hsCRP(mg/L) [3.18 (1.10,11.52) vs 1.78 (0.65,6.46),P＜0.01],fibrinogen(g/L) [3.17 (2.87,3.74) vs 2.97 (2.59,3.50),P=0.002],and uric acid(μmol/L) [360 (302,422) vs 341(283,407),P=0.006] in the moderatesevere OSA group were significant higher than those in the normal-mild OSA group.AHI (correlation coefficient=0.171,R2=0.020,P＜0.01),ODI (correlation coefficient =0.201,R2=0.027,P＜0.01),and TSaO2 ＜ 90％ (correlation coefficient =0.105,R2=0.005,P＜0.01) were positively correlated with hs-CRP;minimal SaO2 (correlation coefficient=-0.100,R2=0.001,P=0.008) and mean SaO2 (correlation coefficient =-0.127,R2=0.006,P＜0.01) were negatively correlated with hs-CRP.Conclusions For patients with ACS,the level of inflammatory markers in the moderate-severe OSA group is significantly higher than that in the normal-mild OSA group.Hs-CRP is significantly associated with the severity of OSA.Diagnosis and monitoring of OSA should be considered in ACS management in the future.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.