ObjectiveTo investigate the spontaneous premature cardiac aging in SHJH^hr mice. MethodsA comparative study was conducted between SHJH^hr mice (SHJH^hr group) and wild-type ICR mice (WT group) at different ages (10 and 24 weeks). Cardiac function was analyzed using a small animal in vivo ultrasound imaging system. After euthanasia, organs were collected and weighed to assess the extent of cardiac atrophy. Cardiac pathological damage was observed using hematoxylin-eosin (HE) staining. Cardiac fibrosis was analyzed using Masson staining. Myocardial cell area was analyzed after wheat germ agglutinin (WGA) staining. The activities of oxidative damage indicators in myocardial tissue, including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), as well as the content of 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured using enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of factors associated with inflammation, fibrosis, and oxidative stress. Colorimetric assay was used to measure malondialdehyde (MDA) levels. ResultsCompared to WT group mice of the same age, 10-week-old mice in the SHJH^hr group showed no significant differences in stroke volume (SV), ejection fraction (EF), fractional shortening (FS), or heart and lung weights. However, at 24 weeks of age, mice in the SHJH^hr group had significantly lower SV, EF, and FS values compared to mice of the same age in the WT group (P<0.05), with no significant change in lung weight but a significant reduction in heart weight (P<0.05). Histological analysis of heart tissue from 24-week-old mice revealed no significant difference in cardiac fibrosis levels between SHJH^hr and WT groups, but WGA staining showed a significant reduction in myocardial cell area in mice in the SHJH^hr group (P<0.05). PCR analysis revealed a significant downregulation of mRNA levels of oxidative stress factors Sod2, Gpx1, and Cat genes (P<0.05). Biochemical assays indicated significantly reduced activities of oxidative damage-related enzymes SOD, GPX, and CAT in myocardial tissue (P<0.05), while the levels of oxidative damage markers 8-OHdG and MDA significantly increased (P<0.05). ConclusionMice in the SHJH^hr group exhibit premature cardiac aging, which may be associated with oxidative stress damage in myocardial tissue.

Objective:To explore the therapeutic efficacy and factors influencing the sequential combination of nucleos(t)ide analogues (NAs) with pegylated interferon alpha (Peg-IFN-α) in the treatment of patients with chronic hepatitis B (CHB).Methods:144 CHB cases with NAs treatment for more than 1 year, HBV DNA < 20 IU/ml, hepatitis B surface antigen (HBsAg) quantification < 3 000 IU/ml, treated with a sequential combination of Peg-IFN-α treatment for 48 to 96 weeks, and followed up were selected from the Fifth Medical Center of the PLA General Hospital between May 2018 and May 2020. Intention-to-treat analysis was used to measure the HBsAg clearance rate at 96 weeks. The Kaplan-Meier method was used to compute the cumulative HBsAg clearance rate at 96 weeks. Univariate and multivariate logistic regression were used to analyze the factors influencing HBsAg clearance at 48 weeks of sequential combination therapy. Univariate and multifactorial COX proportional hazard models were used to analyze the factors influencing HBsAg clearance following 96 weeks of prolonged PEG-IFN-α treatment. The receiver operating characteristic curve was used to assess the predictive value of factors influencing HBsAg clearance. A Mann-Whitney U test was used to compare the measurement data between groups. The count data was compared using the χ2 test between groups. Results:41 (28.47%) cases achieved HBsAg clearance at 48 weeks of sequential combination therapy. The HBsAg clearance rate at 96 weeks was 40.28% (58/144) by intention-to-treat analysis. The Kaplan-Meier method computed that the cumulative HBsAg clearance rate at 96 weeks was 68.90%. Multivariate logistic regression analysis showed that HBsAg quantification at baseline ( OR = 0.090, 95% CI: 0.034-0.240, P < 0.001) and a 24-week drop in HBsAg level ( OR = 7.788, 95% CI: 3.408-17.798, P < 0.001) were independent predictors of HBsAg clearance in CHB patients treated sequentially in combination with NAs and Peg-IFN-α for 48 weeks. Receiver operating characteristic curve analysis showed that the baseline HBsAg quantification [area under the receiver operating characteristic curve (AUC), 0.911, 95% CI: 0.852-0.952)] and 24-week drop in HBsAg level (AUC = 0.881, 95% CI: 0.814-0.930) had equally good predictive value for 48-week HBsAg clearance, but there was no statistically significant difference between the two ( Z = 0.638, P = 0.523). The value of the combination of baseline HBsAg quantification and 24-week drop in HBsAg level (AUC = 0.981, 95% CI: 0.941-0.997) was superior to that of single baseline HBsAg quantification ( Z = 3.017, P = 0.003) and 24-week drop in HBsAg level ( Z = 3.214, P = 0.001) in predicting HBsAg clearance rate at 48 weeks. Multivariate COX proportional hazards model analysis showed that HBsAg quantification at 48 weeks ( HR = 0.364, 95% CI: 0.176-0.752, P = 0.006) was an independent predictor of HBsAg clearance with a prolonged course to 96 weeks of Peg-IFN-α treatment. Conclusion:The HBsAg clearance rate can be accurately predicted with baseline HBsAg quantification combined with a 24-week drop in HBsAg level in patients with CHB who are treated with a sequential combination of NAs and Peg-IFN-α therapy for 48 weeks. Prolonging the course of Peg-IFN-α treatment can enhance the HBsAg clearance rate's capability. An independent predictor of HBsAg clearance is HBsAg quantification at 48 weeks of sequential combination therapy with a prolonged course of 96 weeks of Peg-IFN-α treatment.

As a digestive organ, the liver has the functions of metabolism, synthesis, and detoxification. It is also an immune organ and plays an important role in maintaining anti-infection, autoimmune stability, and anti-tumor. In particular, the liver has unique immunological advantages. Its immune cells can maintain the liver's immune homeostasis and participate in immunoregulation. A variety of immunotherapy is used in clinical trials for the treatment of difficult and critical liver diseases. This review mainly summarizes the recent clinical trials of immunotherapy in chronic hepatitis B, cirrhosis, hepatocellular carcinoma, and autoimmune liver disease.

Objective:To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B.Methods:98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks.Results:During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log 10IU/ml vs. (0.73 ± 0.81) log 10IU/ml, P = 0.017; (1.54 ± 1.27) log 10IU/ml vs. (0.57 ± 0.56) log 10IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion:Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.

Objective To evaluate the effect of denatonium benzoaten on α-smooth muscle actin (α-SMA),subepithelial collagen and airway inflammation in asthmu mice.Methods Forty-five BALB/c mice were divided into 3 groups,normal control group (A group),asthma model group (B group),asthma model+ denatonium benzoaten group(C group);α-SMA detected by using immunohistochemistry,lung sections were stained with Masson to detect subepithelial collagen,HE stain method was used to observe the airway inflammation the images were analyzed with semi-quantitative computer.Results The deposition of α-SMA、subepithelial collagen and inflammation degree in C group was significantly reduced compared with B group,the difference were statistically significant(P＜0.05).Conclusion Denatonium benzoaten can improve airway remodeling in asthmatic mice.

number of goblet cells, mucus secretion and mucin MUC5AC content in lung tissues. Results S100A9 in BALF of group B was (11.89±0.77) ng/mL, S100A9 integrated optical density (IOD) value in airway epithelial cells was 13.96±1.62, PAS stain area /epithelial cell area was (12.53±1.21)%, relative value of MUC5AC / NADPH was 173.91±4.29, all of the above were higher than those of group A [(6.19±0.61) ng/mL, 4.97±0.30, (1.94±0.18)%, 1];S100A9 levels, IOD of S100A9 in airway epithelial cells, PAS stain area / epithelial cell area (%), relative value of MUC5AC / NADPH in group C [(10.69±0.79) ng / ml, 11.80±0.72, (10.61±0.61)%, 94.65±1.59], group D[(9.49±0.99) ng/mL, 10.39±0.59, (8.63±0.62)%, 82.08±1.12], group E [(7.54± 0.42) ng/mL, 5.63±0.84, (4.59±0.87)%, 26.30±1.94] were lower than group B, which showed a dose-dependent reduction and the difference was statistically significant (P<0.05 or P<0.01). Conclusion DB downregulates the expression level of Ca2+-binding protein S100A9 and the mucus secretion amount of the airway goblet cells in rats.

Objective To investigate the effect of fenofibrate on the matrix metalloprotenase-9 (MMP-9) expression and the proliferation of cultured human umbilical vein endothelial cell (HUVECs) induced by oxidized low density lipoprotein(ox-LDL-C).Methods HUVECs cultured in vitro at passage 4 to 9 were used for the experiment.They were divided into control group,ox-LDL-C group (100 mg/L) and ox-LDL-C + fenofibrate group.The cells in ox-LDL-C + fenofibrate group were firstly incubated with 10,50,100 μmol/L fenofibrate respectively for 6 h,then incubated with 100 mg/L ox-LDL-C for another 24 h.MMP-9 expression in supernatant medium was detected by enzyme-linked immuno sorbent assay (ELISA) and cell proliferation was measured by MTT assay.Results Compared with the control group,ox-LDL-C (100 mg/L) could inhibit the proliferation of HUVECs (P ＜ 0.01) and promote the production of MMP-9 of HUVECs.Fenofibrate could inhibit the proliferation of HUVECs induced by ox-LDL-C in a dose-dependent manner (P ＜ 0.01).Fenofibrate (10,50,100 μmol/L) could significantly stimulate the production of MMP-9 of HUVECs induced by ox-LDL-C (P ＜ 0.01).The stimulation effect was dose-dependent.Conclusion Fenofibrate can inhibit the production of MMP-9 in HUVECs induced by ox-LDL-C,promote the proliferation of HUVECs and protect endothelial function in a dose-dependent manner,then may play the role of anti-artherosclerosis besides lipid regulation.

Objective To study the impact of different insulin levels on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM),through analysis of different glycometabolism condition among quinquagenarian population.Methods Subjects enrolled were Beijing habitants who received annual physical examination [ including oral glucose tolerance test (OGTI) ] in the Chinese PLA General Hospital from 2005-2007.According to the OGTT results,the subjects were divided into three groups,including normal glucose tolerance-non-hyperinsulinemia group (NGT-NHIns),IGT-hyperinsulinemia group (IGT-Hins) and IGT-non-hyperinsulinemia group (IGT-NHINS).The prognosis between the year 2009 and 2010 of the three groups was observed.Hyperinsulinemia was diagnosed with fasting serum insulin ≥ 15 mU/L and/or 2-hour serum insulin ≥ 80 mU/L after glucose loading.Results The rate of case number of conversion to T2DM in IGT-NHIns group (42/133) was higher than that in IGT-Hins group (24/154) or NGT-NHIns group (12/126).The HOMA insulin resistance index (HOMAIR) of individuals with IGT-NHIns was lower than that of IGT-Hins [ 0.96 (0.40,3.53 ) vs 2.04 (0.59,23.20),P ＜ 0.05 ],while whole body insulin sensitivity index (WBISI) was higher than that of IGT-Hins [ 7.48 (3.20,31.35 ) vs 3.28 ( 0.86,7.67 ),P ＜ 0.05 ].Modified β-cell function index ( MBCI ) and insulin secretion index (ISI) in IGT-NHIns was poorer than that of IGT-Hins respectively [ 2.57 (0.58,10.98) vs5.17(1.04,65.09); 7.66 (0.99,28.40) vs 17.56 (4.18,96.46),allPvalues ＜0.01].Conclusions The risk of IGT-NHIns progressing into T2DM is higher than that of IGT-Hins. For the prevention of T2DM,individuals with IGT-NHIns should be paid more attention than keeping an eye on IGT-Hins patients.Early control of risk factors could protect β cell function and prevent the progression to T2DM.

Objective To study the correlation between hyperinsulinemia (HIns) and arteriosclerosis in one community in Beijing. Methods Subjects who received arteriosclerosis screening in physical examination annually were studied. All subjects were received 75g oral glucose tolerance test (OGTT) to evaluate glucose metabolic level, and brachial-ankle pulse wave velocity (baPWV) examination to evaluate arteriosclerosis. The correlation between hyperinsulinemia and pulse wave velocity was analyzed. Results Among all the 1046 subjects under investigation, baPWV of subjects with HIns was higher than subjects with normoinsulinemia (NIns) in different glucose metabolism status [normal glucose tolerance, ( 1381.2 ±280. 8) cm/s vs ( 1280. 3 ±218. 7) cm/s; imparied glucose regulation, ( 1557. 5 ±319.3) cm/s vs (1474.7 ±305. 1) cm/s; diabetes, (1764.3 ±476.6) cm/s vs (1664.2 ±374.6)cm/s], especially in subjects with normal glucose tolerance ( P ＜ 0.01 ). The prevalence of cardiovascular risk factors in subjects with HIns was much higher than subjects with NIns ( P ＜ 0.01 ). Multiple logistic regression analysis showed that hyperinsulinemia was the risk factor of arteriosclerosis, and the OR (95%CI) of subjects with HIns was 1.91 (1. 169-3. 105, P ＜0.01 ) as compared to the subjects with NIns. Conclusion The subjects with HIns suffered from much more metabolic risk factors than NIns.Hyperinsulinemia that closely correlated with baPWV was a risk factor of arteriosclerosis.

Objective To compare the difference of cutpoint and clinical significance of HbA1C for the diagnosis of abnormal glucose metabolism in two population groups with different ages.Methods According to oral glucose tolerance test(OGTT),the cutpoint and clinical significance of HbA1C for the diagnosis of type 2 diabetes and impaired glucose regulation(IGR)were investigated in the two population groups.Results The mean HbA1C of 1 064 young subjects in an academy and 1 671 aged subjects in a community were 5.31% ±0.41% and 5.79% ±0.71%,respectively.The cutpoints of HbA1C for diagnosis of diabetes were 5.7%(specificity 86.7%,sensitivity 66.7%)and 5.9%(specificity 73.8%,sensitivity 80.1%)in the two population groups,and 5.6% for diagnosis of IGR (specificity 82.8%,sensitivity 55.8%)and 5.7%(specificity 60.9%,sensitivity 64.3%),respectively.87.8%,78.7%,and 38.5% were diagnosed diabetes by current OGTT criteria at HbA1C levels of ≥5.7%,≥5.9%,and≥6.5%,IGR being 61.6%,39.6%,and 4.1%,and normal glucose tolerance being 24.4%,10.0%,and 0.4%.Conclusion The cutpoints of HbA1C for diagnosis of diabetes and IGR are different in populations with different ages and HbA1C levels.As one of diagnostic criteria for diabetes,HbA1C 6.5% with relatively higher specificity and lower sensitivity must be combined with fasting blood glucose,random blood glucose,and OGTT.