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Objective: To investigate the changes of serum levels of leptin in chronic heart failure (CHF) rats with cachexia and to study its mechanism via leptin receptor expression and leptin signal transduction pathways. Methods: There were 15/60 male SD rats were randomly used as Control group. CHF model was established in rest 45 rats by isoproterenol hydrochloride (ISO) injection as CHF group, n=36;9 rats died. According to body weight changes and echocardiography examination, CHF rats were further divided into 2 groups:cCHF group, the rats with cachexia, n=16 and ncCHF group, the rats with non-cachexia, n=20. Serum levels of leptin and protein levels of janus activating kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling 3 (SOCS3) were examined by ELISA;the expressions of leptin receptor in the myocardial and adipose tissues were observed by immunohistochemistry;mRNA expressions of JAK2, STAT3 and SOCS3 in adipose tissue were detected by RT-PCR. Results: Serum levels of leptin, JAK2, STAT3 and the expressions of JAK2, STAT3 in adipose tissue were higher in both ncCHF and cCHF groups than Control group, P0.05. Serum levels of leptin, SOCS3 and mRNA expression of SOCS3 in cCHF group were lower than ncCHF group, P Conclusions: Increased serum level of leptin was involved in HF occurrence, leptin receptor expression and JAK2/STAT3 signal transduction pathways might be related to CHF combining cachexia in experimental rats.
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Objective To evaluate the efficacy of caudal block with dexmedetomidine mixed with lidocaine for management of perioperative analgesia in children. Methods Thirty pediatric patients, aged 2-6 yr, weighing 8-23 kg, scheduled for elective unilateral high ligation of hernial sac, were equally and randomly assigned into either lidocaine group ( group L ) or dexmedetomidine mixed with lidocaine group ( group DL) using a random number table. Each patient received a single caudal dose of 1% lidocaine 1 ml∕kg in group L. Each patient received a single caudal dose of 1% lidocaine 1 ml∕kg mixed with dexmedetomidine 1 μg∕kg in group DL. Postoperative analgesia was assessed using FLACC scale. When FLACC score ≥4, ibuprofen suspension 10 mg∕kg was given orally. The consumption of ibuprofen was recorded within 8 h after operation. The onset time of caudal block and duration of analgesia were recorded, and adverse effects were observed. Results Compared with group L, the onset time of caudal block was significantly shortened, the duration of analgesia was prolonged, and the requirement for ibuprofen was decreased in group L. There was no significant difference in adverse effects between the two groups. Conclusion Addition of dexmedetomidine 1 μg∕kg to caudal lidocaine can significantly optimize the efficacy of caudal block with lidocaine alone for the management of perioperative analgesia in children.
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Objective To investigate the effect of hepatitis B virus (HBV) on the immune function of natural killer (NK) cells.Methods Healthy human peripheral blood-derived NK cells were cultured alone,or co-cultured with plasmacytoid dendritic cell (pDC) (NK∶ pDC=5∶1) for 48 h with or without HepG 2.2.15-derived HBV.Cell activation was assessed by flow cytometry.The specific enzyme linked immunosorbent assay (ELISA) and intracellular cytokine staining (ICS) were used to determine the cytokine production,the cytotoxic effect of NK cells on the carboxyfluorescein diacetate succinimidyl ester (CFSE)-labelled K562 target cells as well as the granzyme and perforin levels in NK cells.Paired results were analysed using Wilcoxon signed rank test.Results HBV did not affect interleukin (IL)-12/IL-18 and IL-18/interferon α (IFNα)-induced interferon γ (IFNγ) production by NK cells when NK cells were cultured alone (both P＞0.05).However,HBV significantly inhibited pDC-induced IFNγ production by NK cells (146.1 pg/mL),while CpG enhanced pDC-induced IFNγ production by NK cells significantly (1135.4 pg/mL,P=0.0005).HBV did not affect pDC-induced NK cell activation and cytotoxicity to K562 target cells as well as intracellular granzyme and perforin levels.ConclusionHBV does not activate but inhibits pDC-induced NK cell function,which may contribute to the persistence of HBV infection.
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Objective To investigate the expression and function of retinoic acid-inducible gene Ⅰ(RIG-Ⅰ) in monocyte-derived dendritic cells (MoDC) at different stages of hepatitis B virus(HBV)infection and to explore the role of RIG-Ⅰ in the disease progression after HBV infection. Methods Peripheral blood samples were collected from 28 hepatitis B virus-infected persons, including 21 cases of chronic hepatitis B (CHB) and 7 of acute hepatitis B (AHB). Eighteen healthy subjects were recruited as controls. Purified CD14~+ monocytes were isolated by CD14 microbeads. MoDCs were induced from CD14~+ monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 for 7 days, and then were infected with vesicular stomatitis virus (VSV) to stimulate RIG-Ⅰ expression. The mRNA expression levels of RIG-Ⅰ, interferon (IFN )-promoter stimulating factor-1 (IPS-1) and IFN-β at 16 hours and 24 hours after infection with VSV were measured by real-time quantitative polymerase chain reaction (PCR). Data with normal distribution were tested by analysis of variance. Continuous variables between groups were compared using Mann-Whitney U test. Comparison among multiple groups was done by Kruskal-Wallis test. Results The expression levels of RIG-Ⅰ in MoDCs from CHB patients were significantly lower than those in AHB patients and healthy controls at 16 hours (2.44±2.03, 19. 54±3. 15, 21. 48±8. 39, respectively; F=7.451,P=0.002) and 24 hours (2. 68±2. 93, 10. 31 ±3. 88, 14. 01 ±5. 04, respectively, F = 7. 908, P = 0. 001)following VSV stimulation. The IPS-1 levels in both CHB patients and AHB patients were higher than those in healthy controls at 16 hours (2. 05±l. 08, 1. 99±1. 56, 0. 60±0. 31, respectively) F=7.246,P =0.003) and 24 hours (2. 27±2. 16, 3.24 ± 1.21, 1. 08±0. 73, respectively; F= 13. 598, P = 0. 001).Furthermore, the IFN-β expression levels were significantly lower in CHB patients compared to AHB patients and healthy controls at 16 hours and 24 hours after VSV stimulation. Conclusions The expressions of RIG-Ⅰ and IPS-1 in MoDC are abnormal in HBV infected persons, which indicates that RIG-Ⅰ signaling pathway might be blocked by HBV. The impaired function of MoDC may play a role in HBV infection and chronicity.
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Objective To identify the histological features as well as factors influencing the course of HBeAg-negative chronic hepatitis B virus ( HBV)-infected patients with persistently normal alanine amino-transferase (ALT) levels (PNAL). Methods Ninety-eight HBeAg-negative chronic HBV-infected patients with PNAL who underwent percutaneous liver biopsy were recruited from October 2003 to March 2008. The ALT level, HBV markers, HBV DNA level and liver histological changes were detected. Comparison of means was done by t test and single factor analysis of variance. Nonparametric statistics was done by Marm-Whitey U test and Kruskal-Wallis test. Analysis of independent risk factor was done using Logistic model. The dianostic value of ALT level to significant liver histological changes was evaluated by receiver performance curve. Results Twenty-two point four percent and 17.3% of subjects had the histological activity index (HAI)≥4and fibrosis (F) score≥3 respectively. Subgroup analysis showed that subjects with ALT＞0.50 × upper limit of normal (ULN) had a significantly higher rate of HAI≥4 and F score≥3 than those with ALT≤0.50×ULN (HAI≥4:36.4% vs 11.1%, χ2 =8.881, P=0.003;F score≥3:27.3% vs 9.3%, χ2 =5.487, P= 0.019, respectively), and older subjects (more than 45 years old) had a higher proportion of HAI ≥4 than the younger (33.3% vs 13.4%, χ2 =4.923, P=0.027). Multivariate Logistic regression analysis revealed that a decade increase in age was the independent predictor of HAI≥4 (OR=2.410, P=0.023).Receive operating characteristic (ROC) curve showed that 87.0% and 90.7% of subjects with ALT＜0.50× ULN had histological changes of HAI＜4 and F score＜3 respectively. The proportions of HAI≥4 and F score≥3 in subjects with HBV DNA＜1×104 copy/mL were 14.9% and 12.8%, respectively. Conclusions Significant histological changes may be present in part of the subjects with persistently normal ALT and different HBV DNA levels, so that liver biopsy is very important, especially in those with age ＞45 years.Half time the ULN may serve as an appropriate cutoff value of normal ALT level for managing Chinese HBeAg-negative chronic HBV-int'ected patients.