门冬氨酸鸟氨酸联合纳洛酮治疗急性肝性脑病的临床疗效

目的:研究门冬氨酸鸟氨酸与纳洛酮联合治疗急性肝性脑病的临床疗效。方法:选取2012年5月-2013年12月住院的肝性脑病患者48例,随机分为观察组、纳洛酮组和氨基酸组。观察组在常规治疗的基础上给予纳洛酮与门冬氨酸鸟氨酸治疗,纳洛酮组仅给予纳洛酮,氨基酸组仅给予门冬氨酸鸟氨酸治疗,疗程均为7d。观察3组患者治疗的有效情况及前后血氨浓度、肝功能的变化。结果:观察组用药后治疗有效率及清醒时间均优于纳洛酮组和氨基酸组,差异有统计学意义(P<0.05);观察组用药后血氨浓度以及肝功能(ALT、TBIL)也明显优于纳洛酮组和氨基酸组,差异有统计学意义(P<0.05)。结论:纳洛酮与门冬氨酸鸟氨酸联合治疗急性肝性脑病效果显著,能够迅速降低血氨浓度,促进肝功能恢复,值得在临床上推广与应用。     

Oxytocin in the regulation of social behaviours in medial amygdala‐lesioned mice via the inhibition of the extracellular signal‐regulated kinase signalling pathway

The neuropeptide oxytocin (OXT) has been implicated in the pathophysiology of behavioural deficits among patients with autism spectrum disorder (ASD). However, the molecular mechanisms underlying its role in ASD remain unclear. In the present study, a murine model with ASD‐like phenotypes was induced by intra‐medial amygdala injection of N‐methyl‐d ‐aspartate, and it was used to investigate the role of OXT in behaviour regulation. Behavioural tests were performed to verify the ASD‐like phenotypes of N‐methyl‐d ‐aspartate‐treated mice, and the results showed that mice with bilateral medial amygdala lesions presented significant behavioural deficits, including impaired learning and memory and increased anxiety and depression. We also observed a notably decreased level of OXT in both the plasma and the hypothalamus of medial amygdala‐lesioned mice, and the extracellular signal‐regulated kinase (ERK) was activated. Further studies demonstrated that the administration of OXT alleviated ASD‐like symptoms and significantly inhibited phosphorylation of ERK; the inhibitory effect was similar to that of U0126, an ERK signalling inhibitor. In addition, OXT administration modulated the expression of downstream proteins of the ERK signalling pathway, such as cyclic adenosine monophosphate response element binding and c‐fos. Taken together, our data indicate that OXT plays an important role in ameliorating behavioural deficits in an ASD‐like mouse model, which was mediated by inhibiting the ERK signalling pathway and its downstream proteins.     

Individual and combined relationship of serum uric acid and alanine aminotransferase on metabolic syndrome in adults in Qingdao,China

Background and aimsAssociations of alanine aminotransferase (ALT) and serum uric acid (SUA) with metabolic syndrome (MetS) remain controversial. We aimed to explore individual and combined effects of ALT and SUA on MetS in community residents.Methods and resultsA population-based cross-sectional survey involving randomly selected Chinese adults aged 35–74 years was conducted in 2009 in Qingdao, China, and 4642 participants were included in the current study. Based on a combination of SUA and ALT levels in the tertile, subjects were grouped into Group 1-9. The individual and combined relations of SUA and ALT to MetS were analyzed by logistic regression models. The prevalence of MetS was 28.50% in males and 22.30% in females. ALT and SUA were independently associated with MetS and ORs (95% CIs) were 1.55 (1.42–1.70) and 1.92 (1.72–2.14), respectively, after adjusting for potential confounders. With the elevation of ALT and SUA levels, the risk of developing MetS increased. Compared to Group 1, ORs (95% CIs) of combined ALT and SUA for MetS were 2.21 (1.70–2.88), 4.02 (3.10–5.21), 2.19 (1.62–2.97), 2.53 (1.91–3.34), 4.69 (3.60–6.12), 1.76 (1.17–2.64), 3.65 (2.63–5.06) and 7.15 (5.41–9.46) in Group 2–9, respectively.ConclusionsALT and SUA were both related to MetS independently. Combined elevation of ALT and SUA levels could increase the risk of MetS and its components than an elevation in SUA and ALT alone. Therefore, measures should be taken to lower SUA and ALT levels to reduce the risk of having MetS.     

Effects of heparin on hepatic regeneration and function after partial hepatectomy in rats

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Genotype,serum level of hepatitis C virus RNA and liver histology as predictors of response to interferon-α 2α therapy in Japanese patients with chronic hepatitis C

Abstract: To determine whether pretreatment HCV-RNA level, hepatitis C virus genotypes, alanine aminotransferase and histology correlate with subsequent response to interferon-α therapy or not, serum HCV-RNA levels and genotype were determined by branched DNA signal amplification assay and genotype-specific polymerase chain reaction in 43 patients with chronic active hepatitis C. Response to recombinant interferon-α 2α (504 million units in total) was defined as complete and sustained CR→SR, n=12), complete response followed by relapse (CR→Rel, n=17), and no response (NR, n=10), excluding dropouts (n=4). Patients who showed CR→SR had a lower HCV-RNA level (0.438 × 10⁶ eq/ml) compared to CR→Rel (2.452 × 10⁶ eq/ml, p=0.008) and NR (4.882 × 10⁶ eq/ml, p=0.009). A higher proportion of patients with CR→SR had type 2a HCV (67%) compared to the CR→Rel (28%) and the NR (0%). There was a trend for type 1b hepatitis C virus infection to have higher serum HCV-RNA levels. There was no correlation between pretreatment HCV-RNA level and alanine aminotransferase. However, no relation between pretreatment HCV-RNA level and liver histology was observed; a high proportion of patients with CAH2a showed CR→SR, compared to those with CAH2b (p=0.001). Moreover, the patients with CAH2b who had low level hepatitis C virus viremia did not show CR→SR. These data indicate that pre-treatment serum HCV-RNA levels, genotype and liver histology are good predictors of subsequent response to interferon-α therapy in Japanese patients with chronic hepatitis C virus infection.     

The impact of antiviral therapy for HCV on kidney disease: a systematic review and meta-analysis

BackgroundControversy persists about the role of hepatitis C as a risk factor for developing kidney disease in the general population. Some authors have evaluated the effect of antiviral therapy for HCV on the risk of kidney disease.Study Aims and DesignA systematic review of the published medical literature was performed to assess whether antiviral therapy for HCV has an independent impact on kidney survival in the adult general population. A random effects model was used to generate an overall estimate of the risk of kidney disease after anti-HCV therapy across the published studies. Meta-regression and stratified analysis were also carried out.ResultsFifteen studies were eligible (n = 356, 285 patients) and separate meta-analyses were conducted according to the outcome. Pooling studies based on viral responses (n = 7; 34,763 individual patients) demonstrated a relationship between sustained viral response and lower frequency of kidney disease; the overall estimate for adjusted risk of kidney disease was 2.50 (95% CI, 1.41; 4.41) (p = 0.0016) and between-study heterogeneity was found (p-value by Q test = 0.004). Aggregation of studies comparing treated vs untreated cohorts (n = 8, n = 333,312 patients) revealed an association between anti-HCV therapy and lower risk of kidney disease. The overall estimate for adjusted risk of kidney disease across the eight studies was 0.39 (95% CI, 0.25; 0.612) (p = 0.0001). Meta-regression showed that the effectiveness of antiviral therapy in reducing the frequency of kidney disease diminishes as cirrhosis (p = 0.02) and HBV infection (p = 0.0001) increase among HCV-infected individuals.ConclusionsAntiviral therapy for HCV lowers the risk of kidney disease among HCV-infected individuals. Studies to understand the mechanisms underlying this association are ongoing.     

Effect of cytokine gene polymorphism on histological activity index, viral load and response to treatment in patients with chronic hepatitis C genotype 3

AIM: To investigate the association between cytokine gene polymorphism and disease status in chronic hepatitis C genotype 3 by liver biopsy, ALT, HCV RNA levels and response to treatment. METHODS: Patients with chronic hepatitis C genotype 3 were analyzed for single nucleotide polymorphisms of interleukin (IL)-10, IL-1 beta, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) by polymerase chain reaction using sequence-specific oligonucleotide primers. Liver biopsies were assessed by modified histological activity index (HAI) scoring system using a scale of 0-18 for grading the necro-inflammatory activity and 0-6 for staging the fibrosis. HCV RNA levels were determined by bDNA assay. The patients were treated with interferon alpha and ribavirin for 6 mo. Sustained virological response was assessed 6 mo after the completion of the treatment. RESULTS: Out of the 40 patients analyzed, 26 were males. Mean age was 40.5±12.5 years (range 18-65 years). The frequencies of different dimorphic polymorphisms based on single nucleotide substitution were as follows: IL-10-1082 G/A 85%, A/A 12.5%, G/ G 2.5%; IL-10-819 A/C 87.5%, C/C 10%, A/A 2.5%; IL-10-592 C/A 72.5%, C/C 27.5%; IL-1 C 90%, U 10%; IFN-874 T/A 50%, T/T 27.5%, A/A 22.5%; TNF-308 A/G 95%, GIG 5%; TGF-10 T/C 52.5%, C/C 35%, T/T 12.5%. The mean grades of necro-inflammatory activity of different genotypes of IL-10 at promoter site -1082 were A/A = 3.6, A/G = 5.0, and G/G = 10.0 and the difference was significant (P = 0.029). The difference in the stage of disease at a scale of 0-6 was A/A 0.8, A/G 2.3, and G/G 4.0 (P = 0.079). The difference in the HAI seemed to be related to the presence of allele -1082G. For IL-10 -819 genotypes, mean scores of fibrosis were A/A = 6.0, A/C = 2.2, and C/C = 1.0 (P = 0.020) though the inflammatory activity was not much different. No significant differences in HAI were noted among polymorphisms of other cytokines. Moreover, ALT and HCV RNA levels were not significantly different among different cvtokine polymorphisms. There was a significant correlation of HAI and HCV RNA levels with the duration of disease. TGFBBB -10 genotype CC patients had a better end of treatment response than those with other genotypes (P = 0.020). Sustained virological response to the treatment was not influenced by the cytokine polymorphism. No effect of other factors like viral load, degree of fibrosis, gender, steatosis, was observed on sustained virological response in this population infected with genotype 3. CONCLUSION: There is no significant correlation between cytokine polymorphisms and HAI except for the polymorphisms of anti-inflammatory cytokine IL-10, which may influence hepatic inflammatory activity and fibrosis in patients with chronic hepatitis C genotype 3. Sustained virological response in this genotype does not seem to be influenced by cytokine gene polymorphisms.