甲肝病毒在人血白细胞中体外连续传代和在分类白细胞中增殖的研究

1985年我们采用间接免疫荧光法(IF法)检测出甲肝患者外周血白细胞中有甲肝抗原(HAAg)存在,继而又将HAAg阳性白细胞直接种入PLC/PRF/5细胞,分离到两株甲肝病毒(HAV)NJ—3株和H—1株。为了弄清白细胞所携带的病毒究竟仅为吸附吞饮,抑或能在其中复制增殖,我们将分离到的HAV用正常人血白细胞进行体外增殖试验,现将结果报告如下。     

室旁核在剌激猫肾神经传入纤维引起的血压效应中的应用

The purpose of this study is to investigate the role of paraventricular nucleus of the hypothalamus (PVN) and alpha 1 adrenergic receptor of PVN in the pressor responses to stimulation of renal afferent nerve in alpha 1-chloralose-anesthetized cats with carotid sinoaortic denervation and vagotomy. The pressor response to stimulation of renal afferent nerve consisted of a primary and a second components. The primary component response was completely blocked while the second component was not blocked by autonomic blocking agents (hexomethonium and atropine). Bilateral lesions of PVN greatly attenuated the pressor response before and after autonomic blockade. Intracerebroventricular and PVN injection alpha 1, adrenergic antagonist (prazosin) significantly decreased in the pressor response to stimulation of renal afferent nerve. These results indicate that paraventricular nucleus of the hypothalamus and alpha 1 adrenergic receptors in central nervous system, especially in PVN, play an important role in the pressor responses to stimulation of renal afferent nerve.     

Interleukin-28B polymorphisms on the SVR in the treatment of naïve chronic hepatitis C with pegylated interferon-α plus ribavirin: A meta-analysis

There are accurate but inconclusive data on the association between single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B and sustained virological response (SVR) in chronic hepatitis C (CHC). This meta-analysis aimed to derive a more precise estimation of the effects of IL-28B SNPs locus (rs12979860 and rs8099917) on SVR in naïve CHC patients receiving pegylated interferon alpha (PEG-IFN-α) plus ribavirin. Literature search was conducted up to June, 2011, in PubMed, EMBASE and Cochrane Database of Systematic Reviews. A total of 36 studies involving 10912 cases with CHC receiving PEG-IFN-α plus ribavirin met the inclusion criteria. Analyses were stratified either by ethnicity or genotype of hepatitis C virus. In genotype 1/4 patients, rs12979860 CC was associated with high SVR in CHC patients (Caucasian: odds ratio (OR), 4.567; 95% confidence interval (CI), 3.826–5.452; Asian: OR, 4.033; 95%CI, 3.050–5.333; African American: OR, 4.297; 95%CI, 2.168–8.515; Hispanics: OR, 4.350; 95%CI, 2.817–6.717) but had no effect in genotype 2/3. In Caucasian (genotype 1/4: OR, 2.542; 95%CI, 2.108–3.065; genotype 2/3: OR, 1.363; 95%CI, 1.020–1.820) and Asian (genotype 1/4: OR, 5.214; 95%CI, 3.694–7.360; genotype 2/3: OR, 1.785; 95%CI, 1.095–2.910), rs8099917 TT was associated with high SVR in both genotype 1/4 and 2/3. Meta-regression showed that in Caucasians with CHC genotype 1/4, gender male might contribute to the effect of rs12979860 on SVR but advanced fibrosis might weaken this effect. Furthermore, in Asians with CHC genotype 1/4, high baseline viral load and advanced fibrosis might also undermine the effect of rs8099917 on SVR. This meta-analysis suggested that IL-28B rs12979860 CC and rs8099917 TT were associated with high SVR rate in CHC genotype 1/4. In CHC genotype 2/3, rs8099917 TT carriers also had higher SVR.     

MTHFR C677T polymorphism contributes to colorectal cancer susceptibility: evidence from 61 case–control studies

Methylenetetrahydrofolate reductase (MTHFR) is believed to be involved in folate metabolism which plays a critical role in carcinogenesis. To date, many case-control studies have investigated the association between MTHFR C677T polymorphism and colorectal cancer risk. However, the results were inconsistent. In order to derive a more precise estimation of the association, we conducted this meta-analysis. This meta-analysis recruited 61 published studies which were selected by a search of PubMed up to 31st September 2011, including 16,111 colorectal cancer cases and 23,192 controls. We used crude odds ratios (ORs) with 95?% confidence intervals (CIs) to assess the association between MTHFR C677T polymorphism and colorectal cancer susceptibility. Our results showed that MTHFR C667T polymorphism contributed to the decreased colorectal cancer risk in overall population (for TT vs. CC: OR?=?0.89, 95?% CI?=?0.82-0.97; for TT vs. CT/CC: OR?=?0.88, 95?% CI?=?0.83-0.92). In subgroup analysis by ethnicity, the results also indicated a correlation between the T allele of MTHFR C667T and the colorectal cancer risk in Asian population (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.69-0.97; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.74-0.90). Additionally, the correlation was also observed in male subgroup in sub-analysis by gender (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.71-0.93; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.71-0.92). In summary, our meta-analysis strongly indicated the MTHFR C667T polymorphism was associated with a reduced risk of CRC.     

IL‐1β and TNF‐α induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase

Glutaminase 1 is the main enzyme responsible for glutamate production in mammalian cells. The roles of macrophage and microglia glutaminases in brain injury, infection, and inflammation are well documented. However, little is known about the regulation of neuronal glutaminase, despite neurons being a predominant cell type of glutaminase expression. Using primary rat and human neuronal cultures, we confirmed that interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α), two pro‐inflammatory cytokines that are typically elevated in neurodegenerative disease states, induced neuronal death and apoptosis in vitro. Furthermore, both intracellular and extracellular glutamate levels were significantly elevated following IL‐1β and/or TNF‐α treatment. Pre‐treatment with N‐Methyl‐d ‐aspartate (NMDA) receptor antagonist MK‐801 blocked cytokine‐induced glutamate production and alleviated the neurotoxicity, indicating that IL‐1β and/or TNF‐α induce neurotoxicity through glutamate. To determine the potential source of excess glutamate production in the culture during inflammation, we investigated the neuronal glutaminase and found that treatment with IL‐1β or TNF‐α significantly upregulated the kidney‐type glutaminase (KGA), a glutaminase 1 isoform, in primary human neurons. The up‐regulation of neuronal glutaminase was also demonstrated in situ in a murine model of HIV‐1 encephalitis. In addition, IL‐1β or TNF‐α treatment increased the levels of KGA in cytosol and TNF‐α specifically increased KGA levels in the extracellular fluid, away from its main residence in mitochondria. Together, these findings support neuronal glutaminase as a potential component of neurotoxicity during inflammation and that modulation of glutaminase may provide therapeutic avenues for neurodegenerative diseases.     

Accurate Determination of Coulombic Efficiency for Lithium Metal Anodes and Lithium Metal Batteries

Lithium (Li) metal is an ideal anode material for high energy density batteries. However, the low Coulombic efficiency (CE) and the formation of dendrites during repeated plating and stripping processes have hindered its applications in rechargeable Li metal batteries. The accurate measurement of Li CE is a critical factor to predict the cycle life of Li metal batteries, but the measurement of Li CE is affected by various factors that often lead to conflicting values reported in the literature. Here, several parameters that affect the measurement of Li CE are investigated and a more accurate method of determining Li CE is proposed. It is also found that the capacity used for cycling greatly affects the stabilization cycles and the average CE. A higher cycling capacity leads to faster stabilization of Li anode and a higher average CE. With a proper operating protocol, the average Li CE can be increased from 99.0% to 99.5% at a high capacity of 6 mA h cm^?2 (which is suitable for practical applications) when a high‐concentration ether‐based electrolyte is used.     

Inference of patient‐specific subpathway activities reveals a functional signature associated with the prognosis of patients with breast cancer

Breast cancer is one of the most deadly forms of cancer in women worldwide. Better prediction of breast cancer prognosis is essential for more personalized treatment. In this study, we aimed to infer patient‐specific subpathway activities to reveal a functional signature associated with the prognosis of patients with breast cancer. We integrated pathway structure with gene expression data to construct patient‐specific subpathway activity profiles using a greedy search algorithm. A four‐subpathway prognostic signature was developed in the training set using a random forest supervised classification algorithm and a prognostic score model with the activity profiles. According to the signature, patients were classified into high‐risk and low‐risk groups with significantly different overall survival in the training set (median survival of 65 vs 106 months, P = 1.82e‐13) and test set (median survival of 75 vs 101 months, P = 4.17e‐5). Our signature was then applied to five independent breast cancer data sets and showed similar prognostic values, confirming the accuracy and robustness of the subpathway signature. Stratified analysis suggested that the four‐subpathway signature had prognostic value within subtypes of breast cancer. Our results suggest that the four‐subpathway signature may be a useful biomarker for breast cancer prognosis.