To explore novel antifatigue agents targeting with AMPA receptor, 10 compounds were synthesized and their structures were confirmed by 1H NMR, ESI-MS and elemental analysis. 1-BCP was treated as the leading compound. The antifatigue activities were evaluated by weight-loaded forced swimming test, and the AMPA receptor binding affinities were tested with radioligand receptor binding assays. The results unveiled that 5b appeared to possess potent antifatigue activities and high affinity with AMPA receptor, which deserved further studies.

Objective: To investigate the relationship between long-, short-term systolic blood pressure variability (SBPV) and renal damage in elder population. Methods: Our research was conducted in the 3rd physical examination of healthy population from Kailuan group by cohort study. Cluster sampling was used by 25% ratio in subjects≥60 years of age to monitor their 24-hour ambulatory blood pressure and finally, 2464/3064 participants with inclusion criteria were recruited. SBPV indexes as standard deviation of systolic blood pressure (SSD), variability independent of the mean (VIM), maximum-minimum difference (MMD) and average real variability (ARV) were examined; renal damage indexes as estimated glomerular filtration rate (eGFR) and microalbuminuria (ALBU) were detected. Relationships between different long-term, short-term SBPV indexes and eGFR, ALBU were studied by multi-liner regression analysis. Results:①The mean age of 2464 participants was (67.41 ± 6.05) years including 1667 (67.7%) male and 797 (32.3%) female.②Multi-liner regression analysis indicated that different long-term SBPV indexes were not related to eGFR and ALBU; 24h SBPV in all 4 indexes and day-time SSD, MMD, ARV were negatively related to eGFR; 24h ARV and day-time MMD, ARV were positively related to ALBU; night-time SBPV indexes were not related to eGFR and ALBU.Conclusion: Different short-term SBPV indexes were, at certain point related to eGFR and ALBU

OBJECTIVETo investigate the distribution and major influencing factors of annual systolic blood pressure variability from a large population cohort.

METHODSIn this prospective cohort study, data from Kailuan Group employees who attended all 4 physical examinations ( taken in June 2006 to October 2007, June 2008 to October 2009, June 2010 to October 2011, June 2012 to October 2013, respectively) were analyzed (32 959 males and 10 401 females, mean age: (48.2 ± 11.5) years old). Systolic blood pressure variability was defined as the standard deviation (SSD) and the coefficient of variation (SCV) of systolic blood pressure of 4 physical examinations. Multivariate linear regression analysis was used to determine the related influencing factors of SSD and SCV.

RESULTS(1) The mean of SSD and SCV for this cohort was 10.91 mmHg (1 mmHg = 0.133 kPa) and 8.34%, respectively. SSD and SCV increased in male and female with increasing age (both P < 0.001). (2) Multiple linear regression analysis showed that systolic blood pressure (β = 0.225, P < 0.001), age (β = 0.163, P < 0.001), fasting blood glucose (β = 0.038, P < 0.001), the use of anti-hypertensive drugs (β = 0.038, P < 0.001), sex (β = 0.038, P < 0.001), smoking (β = 0.025, P < 0.001), alcohol drinking (P = -0.022, P < 0.001), physical exercise (β = -0.018, P = 0.001), high-sensitivity c-reactive protein (β = 0.016, P = 0.001) body mass index (β = -0.011, P = 0.018) were related to SSD. Age (β = 0.139, P < 0.001), sex (β = 0.055, P < 0.001), systolic blood pressure (β = 0.047, P < 0.001), fasting blood glucose (P = 0.033, P < 0.001), drinking (β = -0.030, P < 0.001), body mass index (β = -0.026, P < 0.001), the use of anti- hypertensive drugs (β = 0.026, P < 0.001), smoking (β = 0.024, P < 0.001), physical exercise (β = -0.015, P = 0. 001), high-sensitivity c-reactive protein (β = 0. 014, P = 0. 001) were related to SCV.

CONCLUSIONSSSD and SCV increase with increasing age. Systolic blood pressure, age, fasting blood glucose, the use of anti-hypertensive drugs, sex, smoking, drinking, physical exercise, high-sensitivity c-reactive protein, body mass index are major influencing factors for SSD. Age, sex, systolic blood pressure, fasting blood glucose, alcohol drinking, body mass index, the use of anti-hypertensive drugs, smoking, physical exercise, high-sensitivity c-reactive protein are major influencing factors for SCV.

Alcohol Drinking ; Antihypertensive Agents ; Blood Pressure ; Body Mass Index ; C-Reactive Protein ; Cohort Studies ; Exercise ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Smoking

Objective: To investigate the changes of cardiovascular health indicator and arteriosclerosis in middle and elder population.
Methods: A total of 4190 subjects with the average age of (49.78 ± 9.74) years by 3 physical examinations in Kailuan group from 2006 to 2011 were randomly stratiifed for arm ankle arterial pulse wave velocity (baPWV) examination. According to 7 AHA cardiovascular health indicators of non-smoking, normal BMI, active excise, healthy diet, normal cholesterol, blood pressure and fasting blood glucose, each indicator had 3 conditions as ideal, general and poor by scores of 2, 1 and 0 respectively. Based on the 1st and 3rd physical examinations, the changes of cardiovascular health scores (△CHS), the subjects were divided into 8 groups as△CHS≤-4,-3,-2,-1, 0, 1, 2 and△CHS≥3, n=241, 368, 611, 855, 911, 647, 354 and 203 respectively. The impacts of△CHS on baPWV values were studied by liner and Logistic regression analyses.
Results: As△CHS increased by △CHS ≤ -4, -3,-2,-1,0,1, 2 and△CHS ≥ 3, the baPWV values were decreased accordingly by cm/s as (1590.78 ± 17.93), (1566.4 ± 14.5), (1552.83 ± 11.25), (1536.59 ± 9.51), (1508.85 ± 9.21), (1499.81 ± 10.93), (1485.92 ± 14.82) and (1475.85 ± 19.57) respectively. Multiple linear regression analysis showed that with adjusted confounding factors, as△CHS increasing 1 score, baPWV increasing 15.58 cm/s (B=15.58, P<0.001). Logistic regression analysis indicated that with adjusted confounding factors, as△CHS increasing 1 score, the risk for arteriosclerosis occurrence was decreased by 14%(OR=0.86, 95%CI 0.83-0.90).
Conclusion: △CHS was negatively related to baPWV in middle and elder subjects, improving cardiovascular health indicator may decrease arteriosclerosis occurrence.

Objective To explore the risk factors for lower extremity amputation in patients with diabetic foot.Methods The clinical data of 1 771 patients with diabetic foot at the Air Force General Hospital of PLA from November 2001 to April 2015 were retrospectively analyzed.The patients were divided into the non-amputation and amputation groups.Within the amputation group , subjects were further divided into the minor and major amputation subgroups.Binary logistic regression analyses were used to assess the association between risk factors and lower extremity amputation.Results Among 1 771 patients with diabetic foot , 323 of them ( 18.24%) were in the amputation group ( major amputation: 41; minor amputation:282 ) and 1 448 ( 81.76%) in the non-amputation group.Compared with non-amputation patients, those in the amputation group had a longer hospital stay and higher estimated glomerular filtration rate(eGFR)levels.Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), C-reaction protein (CRP), ESR, ferritin, fibrinogen and WBC levels of the amputation group were higher , while hemoglobin albumin, transferrin, TC, TG, HDL-C and LDL-C were lower than those of the non-amputation group (all P<0.05 ).The proportion of hypertension ( 52.48% vs 59.98%) , peripheral vascular disease ( PAD ) (68.11% vs 25.04%), and coronary heart disease (21.33% vs 28.71%) were different between the amputation and non-amputation groups (all P<0.05).Multivariable logistic regression analyses showed that Wagner′s grade , PAD and CRP were the independent risk factors associated with lower extremity amputation in hospitalized patients with diabetic foot.Conclusion Wagner′s grade, ischemia of lower limbs and infection are closely associated with amputation of diabetic foot patients.

Objective: To explore the predictive value of inlfammatory factors on all cause mortality in normal population.
Methods: In our prospective cohort study, a total of 83,228 subjects from physical examination of Kailuan group from 2006-07 to 2007-10 were enrolled, nobody had acute inlfammation. The death information was collected once per year and the last follow-up was conducted in 2013-12-31. According to baseline levels, white blood cells (WBC), ratio of neutrophil/lymphocyte ratio (N/L) and C-reactive protein (CRP) were respectively divided into 4 Quartile groups; all cause mortality was compared among different groups and their risks were studied by multi-Cox regression analysis.
Results: The average follow-up time was 6.9 years. All cause mortality in Quartile 1, Quartile 2, Quartile 3 and Quartile 4 groups for WBC were 4.2%, 4.5%, 4.5% and 5.0% respectively; for N/L were 3.3%, 3.6%, 4.5% and 6.7% respectively; for CRP were 3.0%, 3.6%, 4.8% and 6.8% respectively. Multi-Cox regression analysis indicated that with adjusted age, gender, waist and other confounders, by elevation of WBC, N/R and CRP, the risks of all cause mortality were increased accordingly, and the risks in Quartile 4 groups were higher than those in Quartile 1 groups as for WBC, it was 1.17-time (95% CI 1.06-1.29);for N/L, it was 1.44-time (95% CI 1.31-1.59); for CRP, it was 1.33-time (95% CI 1.20-1.47) respectively.
Conclusion: Elevated WBC, N/R and CRP are independent risk factors for all cause mortality in normal population.

Objective: To explore the relationship between longitudinal trajectory of systolic blood pressure (SPB) and atrial fibrillation (AF) in Kailuan group population. Methods: Our study cohort consisted of 40727 participants with the specific criteria in Kailuan group, Tangshan. SAS Proc Traj procedure was used to identify longitudinal trajectories of SPB throughout 2006-2007, 2008-2009 and 2010-2011. There were 5 longitudinal trajectories generated: Low-stable group,n=10950, Moderate-stable group, n=19158, Moderate-high stable group,n=3713, High-moderate stable group,n=4702 and High stable group,n=2181. Log-rank test was performed to compare AF incidence throughout 2012-2013 and 2014-2015 by physical examination among different groups; Multi Cox regression analysis was conducted to study the relationship among different SBP longitudinal trajectories and AF occurrence. Results:①The mean age of participants was (51.81±11.54) years including 30693 (75.4%) male.②AF occurrence rates in Low-stable, Moderate-stable, Moderate-high stable, High-moderate stable and High stable groups were 0.1%, 0.2%, 0.5%, 0.5% and 0.6% respectively, allP<0.05.③Multi Cox regression analysis presented that with adjusted confounding factors, compared with the patients in Low-stable group, Moderate-high stable, High-moderate stable and High stable SBP longitudinal trajectories were the risk factors for new AF occurrence (HR=7.58, 95% CI 2.08-27.73), (HR=5.30, 95% CI 1.88-14.95) and (HR=8.52, 95% CI 1.96-37.09) respectively, allP<0.05. With excluded history of myocardial infarction/stroke, the sensitivity study showed the similar result with the major research trend. Conclusion: Elevated long trajectory of SPB was the risk factor for new AF occurrence in Kailuan group population.

ObjectiveTo investigate the influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). MethodsClinical data were collected from 240 HBV-ACLF patients without liver transplantation who were admitted To The Second Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2019, and the patients were divided into groups according to survival on days 28 and 90 after admission (28-day survival group with 164 patients and 28-day death group with 76 patients; 90-day survival group with 140 patients and 90-day death group with 100 patients). The data collected included predisposing factors, liver function parameters, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and complications. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC), and a multivariate logistic regression analysis was used to investigate the risk factors for the short-term prognosis of HBV-ACLF. ResultsThe main predisposing factors of HBV-ACLF included spontaneous activation of HBV (55.6%) and HBV activation caused by the withdrawal of or resistance to nucleoside analogues (25.2%). There were significant differences in age, prothrombin time activity (PTA), neutrophil-lymphocyte ratio (NLR), serum sodium, MELD score, MELD-Na score, and total bilirubin (TBil) at baseline between the 28-day survival group and the 28-day death group (Z=-2.400,-6.015, -5.070, -5.103, -5.044, -7.430, and -6.637, all P＜0.05), and there were also significant differences in age, PTA, NLR, serum sodium, MELD score, MELD-Na, TBil, and cholesterol at baseline between the 90-day survival group and the 90-day death group (Z=-2.205, -7.728, -3.335, -4.015, -6.053, -7.908, -6.655, and -3.607, all P＜0.05). The multivariate logistic regression analysis showed that TBil ＞260.20 mmol/L (odds ratio ［OR］=4.572, 95% confidence interval ［CI］: 1.321-15823, P＜0.05), PTA ＜24.8% (OR=8.934, 95%CI: 3.026-26.374, P＜0.05), NLR＞5.63 (OR=2.632, 95%CI: 1.126-6.152, P＜0.05), serum sodium ＜130.8 mmol/L (OR=27.467, 95%CI: 6.113-123.423, P＜0.05), MELD score ＞17.84 (OR=4.303, 95%CI: 1.048-17.663, P＜0.05), and MELD-Na score ＞25.1 (OR=3.453, 95%CI: 1.614-7.387, P＜0.05) were independent risk factors for 28-day survival; TBil＞260.20 mmol/L (OR=5.148, 95%CI: 1.918-13.822, P＜0.05), PTA ＜25.5% (OR=15.718, 95%CI: 5.161-47.866, P＜0.05), serum sodium ＜135.3 mmol/L (OR=10.080, 95%CI: 3.244-31.323, P＜005), MELD score ＞17.84 (OR=11.157, 95%CI: 2.580-48.254, P＜0.05), MELD-Na score ＞25.1 (OR=4.391, 95%CI: 2057-9.372, P＜0.05) were independent risk factors for 90-day survival. Among the 240 patients, 160 (66.7%) experienced infection within 90 days, among whom 140 had bacterial infection, 12 had viral infection, and 8 had fungal infection. The 160 patients with infection had a significantly higher 90-day mortality rate than the patients without infection (46.3% vs 32.5%, χ2=6.720, P=0.010). Of all 240 patients, 176 had ascites, 44 had pleural effusion, 36 had acute renal injury, 60 had hepatic encephalopathy, and 12 had gastrointestinal bleeding within 28 days, and there were significant differences in the proportion of patients with acute renal injury, grade Ⅲ-Ⅳ hepatic encephalopathy, or gastrointestinal bleeding between the 28-day survival group and the 28-day death group (χ2=64.088，29811，7.797，all P＜0.05). ConclusionTBil, PTA, serum sodium, MELD score, and MELD-Na score at baseline are independent risk factors for the 28- and 90-day prognosis of HBV-ACLF. Liver inflammation and necrosis caused by HBV activation may be the initiating factor for ACLF, and infection, acute renal injury, hepatic encephalopathy, and gastrointestinal bleeding are the main complications affecting the prognosis of patients.

Primary liver cancer is one of the common malignant tumors and its mortality ranks third in the world. Because there are no obvious symptoms in the early stage of liver cancer, most patients are diagnosed as advanced stage, without the opportunity of surgical resection. The authors report a case of hepatocellular carcinoma with portal vein tumor thrombus, which reduced significantly after hepatic artery infusion chemotherapy combined with bevacizumab and atezolizumab, showing the safety and efficacy.

Objective To assess the efficacy of tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients receiving antiviral therapy for three years. Methods A total of 157 CHB patients treated with TDF alone for ≥3 years from January 2015 to August 2020 in the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively studied. The patients were divided into HBeAg-positive and HBeAg-negative groups based on their baseline HBeAg levels. The data of serum HBV DNA and HBsAg levels at baseline, the first, second and third year of treatment were collected to analyze the dynamic changes. The t -test was used to compare continuous variables with normal distributions between two groups, while the Mann-Whitney U test was used to compare continuous variables with non-normal distribution between two groups. Repeated measurement data with non-normal distribution were first transformed into logarithms and the intra- or between-group comparison was performed using repeated measures analysis of variance. The chi-square test or Fisher exact test was used to compare categorical variables between groups. Results HBV DNA clearance rate in HBeAg-positive patients was significantly lower than that in HBeAg-negative patients during the first and second years of TDF treatment (1st year: 65.8% vs 81.0%, χ 2 =4.676, P < 0.05; 2nd year: 87.7% vs 98.8%, Fisher exact test, P < 0.05). When TDF treatment was given for three years, there was no significant difference in HBV DNA clearance rates (97.3% vs 100%, Fisher exact test, P > 0.05). The baseline HBsAg levels in HBeAg-positive and HBeAg-negative patients were 10 633.6 (2 084.8-24 005.7) IU/mL and 1 402.8 (311.0-2 863.5) IU/mL, respectively, and decreased to 1 534.9 (912.7-5 885.9) IU/mL and 677.8 (119.4-1 974.8) IU/mL after 3 years of TDF treatment, with a significant difference between two groups ( F =25.456, P < 0.001). In HBeAg-positive patients, the median decline value of HBsAg level was significantly higher in the first year [1 856.5 (158.4-12 103.1) IU/mL] than in the second year [879.8 (130.5-2 382.5) IU/mL] or the third year [479.9 (95.0-1 662.4) IU/mL] ( F =10.972, P < 0.001), while there was no significant difference in HBeAg-negative patients ( F =0.513, P > 0.05). In addition, after 3 years of TDF treatment, 59.2% of patients achieved HBsAg < 1500 IU/mL, with a HBsAg negative rate of 1.3%. Conclusion After 3 years of TDF treatment, all HBeAg-negative CHB patients can achieve HBV DNA negative conversion; for HBeAg-positive CHB patients, 97.3% of them achieved HBV DNA negative conversion, while 2.7% of them were still HBV DNA detectable. The HBsAg level declined over treatment time, and the decline rate of HBsAg level in HBeAg positive patients showed a trend of "first fast and then slow". After 3 years of TDF treatment, 59.2% of patients achieved HBsAg < 1500 IU/mL.