Application of oxaliplatin in combination with epirubicin in transcatheter arterial chemoembolization in the treatment of primary liver carcinoma.

Many cases of liver carcinoma miss the opportunity of surgical treatment because of hidden onset and delayed diagnosis. In recent years, interventional treatment has gradually become a non-surgical method for treating liver carcinoma. To discuss the effects of oxaliplatin in combination with epirubicin in the treatment and its influence on prognosis, this study randomly selected 218 advanced primary liver carcinoma patients from Binzhou People’s Hospital, Binzhou, China and divided them into a control group (n=109) and an observation group (n=109). Patients in both groups were given interventional treatment. Patients in the control group were perfused with oxaliplatin, while patients in the observation group were perfused with oxaliplatin and epirubicin. The effectsat 6-month and 12-month survival rates were compared between the two groups. The results demonstrated that the overall effective rate and clinical benefit rate of the observation group were much higher than those of the control group (30.3% vs 11.9%; 79.8%; vs 44.3%) (P less than 0.05). The serum Alpha Fetal Protein (AFP) and Carcino Embryonie Antigen (CEA) levels of the observation group were much lower than those of the control group; the Karnofsky performance score of the observation group was much lower than that of the control group; the two differences had statistical significance (P less than 0.05). The 6-month survival rate of the observation group was 91.67%, higher than that of the control group (86.11%) (P>0.05). The 12-month survival rate of the observation group was 83.33%, much higher than that of the control group (61.11%) (P less than 0.05). The difference of the incidence of adverse reactions between the two groups had no statistical significance (P>0.05). Thus, it can be concluded that oxaliplatin in combination with epirubicin can improve survival quality, extend survival time, and decrease the serum AFP and CEA levels in the treatment of primary liver carcinoma, with definite effects but without aggravating toxic and side effects. Therefore, the therapy has important clinical value.

[Outcome comparison of different therapy procedures in surgical high-risk elderly patients with severe aortic stenosis].

Objective: To compare the outcome of surgical high-risk elderly patients with severe aortic stenosis(SAS) treated by different therapy procedures, including transcatheter aortic valve implantation(TAVI), surgical aortic valve replacement(SAVR), and drug therapy. Methods: We retrospectively analyzed the clinical data of 242 surgical high-risk elderly (age ≥65 years old) SAS patients hospitalized in Fuwai Hospital between September 2012 and June 2015. According to the treatment method, patients were divided into TAVI group (81 cases), SAVR group (59 cases) and drug therapy group (102 cases). The primary end point was all-cause mortality at 1 year post procedure, and secondary end point included cardiac function class(NYHA), vascular complication, valvular function, non-fatal myocardial infarction, new atrial fibrillation, stroke, bleeding, pacemaker implantation, acute renal failure, and readmission. We used the Kaplan-Meier method to estimate survival function based on follow up data and survival was compared between groups with the use of the log-rank test. Results: (1) In the baseline data, there were statistically significant difference among 3 groups for the age, left ventricular ejection fraction, cardiac function class Ⅲ and Ⅳ, rates of combined diabetes, chronic renal failure, mild and moderate mitral regurgitation (P<0.01 or 0.05). The risk score of the Society of Thoracic Surgeons(STS) was 7.28±4.98 in the TAVI group, and 5.67±3.49 in the SAVR group(P=0.036). (2) The perioperative rates of pacemaker implantation(11.3%(9/81) vs. 0, P=0.025) and mild paravalvular regurgitation(29.6%(24/81) vs.1.7%(1/59), P<0.001) were significantly higher in TAVI group than in SAVR group.(3)The rate of rehospitalization was significantly lower in TAVI group than in SAVR group(3.0%(2/67) vs. 22.7%(10/44) P=0.005) and the rate of pacemaker implantation was significantly higher in TAVI group than in SAVR group(17.5 (12/67) vs. 0, P=0.008) after 1 year. The rates of death from any cause in the TAVI (5.8%(4/67)) and SAVR group (11.4%(5/44)) were significantly lower than that in the drug therapy group (54.9%(50/91), both P<0.05) after 1 year and was similar between TAVI group and SAVR group(P=0.622). (4) The rates of cardiac function classⅠandⅡ increased and Ⅲ and Ⅳ decreased in TAVI and SAVR group after 1 year when compared with base line(P<0.001). The rates of cardiac function class Ⅱ, and Ⅲ increased , class Ⅰ and Ⅳ decreased in drug therapy group after 1 year compared with base line (P=0.020). (5)The survival rates after 1 year were significantly higher in the TAVI group and SAVR group than in the drug therapy group(log-rank test, P<0.001), and the difference was similar between TAVI group and SAVR group (log-rank test, P=0.062). Conclusion: In surgical high-risk elderly patients with SAS, the prognosis of drug therapy was poor, and TAVI and SAVR were associated with similarly improved rates of survival after 1 year, although there were significant differences in periprocedural complications between TAVI and SAVR groups.

The effects of bortezomib alone or in combination with 5-fluorouracil on proliferation and apoptosis of choriocarcinoma cells.

PURPOSE: To investigate the effects of bortezomib alone and in combination with 5-fluorouracil (5-FU) on proliferation and apoptosis in the human choriocarcinoma cell line JEG-3. MATERIALS AND METHODS: Cells were treated with bortezomib, 5-FU or with a combination. Proliferation and apoptosis were measured. NF-iB protein expression was examined using immunofluorescence. RESULTS: Following treatment with ten nM bortezomib, rates of apoptosis were significantly higher than controls (p < 0.05) and NF-kB expression increased. 5-FU at 0.025 µg/ml or 0.25 µg/ml resulted in 60.1 ± 0.4% and 67.0 ± 0.2% growth inhibition, respectively, an increase compared to individual treatment (p < 0.05). Apoptosis in cells treated with bortezomib +5-FU was significantly higher than either treatment alone (p < 0.05). Inhibition of proliferation by the combination treatment was synergistic. CONCLUSION: Bortezomib alone or in combination with 5-FU inhibited JEG-3 cell proliferation and induced apoptosis by increasing NF-kB expression. Combination treatment exerted synergistic effects on growth inhibition.

Analysis of risk factors of stage IV gastric cancer from the SEER database.

INTRODUCTION: Gastric cancer is the fourth most common cancer in the world. By the time the patients are diagnosed with stage IV gastric cancer, many patients already have distant metastases. There is no unified systemic treatment plan in existence. The use of gastrectomy is ambiguous in patients with stage IV gastric cancer. The objective of this study was to evaluate the beneficial outcome of gastrectomy in patients with stage IV gastric cancer. METHODS: Clinical information of patients with gastric cancer from 2000 to 2010 in the Surveillance, Epidemiology, and End Results database were extracted and analysed. The risk factors for stage IV gastric cancer were also analysed. RESULTS: We observed that the median survival time for patients after surgery was greater than that for patients not treated surgically. The five-year survival rate for chemotherapy patients was higher than that of non-chemotherapeutic patients. Patients who receive both chemotherapy and surgery could achieve a more significant survival benefit. The risks following gastrectomy (partial, subtotal, hemi-) were lower than those of other surgical procedures, which provided guidance on the choice of surgical method. The numbers of regional lymph node metastasis were found to be related to prognosis. CONCLUSIONS: In patients with stage IV gastric cancer, gastrectomy (partial, subtotal or hemi) should be selected when surgery is necessary. The number of regional lymph node metastasis could be considered as a prognostic factor for patients with stage IV gastric cancer and lymph node dissection could reduce the risk of patients undergoing surgery.

Seroepidemiology of Neospora caninum and Toxoplasma gondii infection in yaks (Bos grunniens) in Qinghai, China.

Neospora caninum is a protozoan parasite and is closely related to Toxoplasma gondii, but they are antigenically different. N. caninum and T. gondii infection in a variety of animals such as cattle, dogs, and cats has been reported, but there is little information on the infection of these parasites in domestic yaks. Seroprevalence of antibodies to T. gondii and N. caninum in yaks (Bos grunniens) from eight regions of Qinghai, China were investigated by the indirect agglutination test (IAT) and ELISA, respectively. A total of 112 (11.8%) of 946 serum samples were positive for antibodies to T. gondii, and 21 samples (2.2%) were positive to N. caninum. Two of the yaks had antibodies to both parasites. There was no apparent association of T. gondii infection with age of the animals. The results indicate that T. gondii infection is prevalent in Chinese yaks in most parts of Qinghai province and N. caninum infection rate in the same species is relatively low. This is the first large study showing the infection of T. gondii and N. caninum in domestic yaks.

Interaction of a lens cell transcription factor with the proximal domain of the mouse gamma F-crystallin promoter.

The elements regulating lens-specific expression of the mouse gamma F-crystallin gene were examined. Here we show that mouse gamma F-crystallin sequences -67 to +45 contain a low basal level of lens-specific promoter activity and that sequences -67 to -25, which are highly conserved among different gamma-crystallin genes, are able to function as a strong transcriptional activator when duplicated and placed upstream of the TATA box. We also show that nuclear factors from lens and nonlens cells are able to form different complexes with sequences centered at -46 to -36 and demonstrate that binding of the factor from lens cells correlates with lens-specific promoter activity of the mouse gamma F-crystallin gene.

Mechanism of the high coagulation state of breast cancer tissue factor.

OBJECTIVE: We conducted this study to analyze the mechanism behind the high coagulation state induced by circulating plasma microparticle tissue factor (MP-TF) in patients with breast cancer. PATIENTS AND METHODS: 87 cases of breast cancer patients (10 cases of TNM stage I, 16 cases of II, 32 cases of III, 29 cases of IV; 8 cases of pathological type in situ carcinoma, 15 cases of ductal carcinoma, 64 cases of invasive cancer) were used as the observation group and 20 cases of benign breast lesions were used as the control group to compare MP-TF levels of plasma and coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-dimer body (D-D) level and NF-κB signaling pathway index including P50, p65, TAK1 and IκBα levels. RESULTS: The plasma MP-TF level in the observation group was significantly higher than that in control group, and the level of MP-TF in the observation group increased with an increase in depth of TNM stage and tumor invasion; differences were statistically significant (p<0.05). In the observation group, the plasma PT and APTT were shortened, and the levels of FIB and D-D were increased; the differences were statistically significant (p<0.05). In the observation group, the levels of P50, p65, TAK1, IκBαin circulating blood were higher than those in control group; the differences were statistically significant (p<0.05). After the Pearson test, the plasma levels of MP-TF in patients with breast cancer were negatively correlated with PT and APTT, and positively correlated with FIB, D-D values and the levels of p50, p65, TAK1 and IκBα (4 p<0.05). CONCLUSIONS: MP-TF can lead to high blood coagulation in patients with breast cancer through the activation of NF-κB signaling pathway, which may become a new target for the intervention of the disease.

Identification of a long stretch of homopurine.homopyrimidine sequence in a cluster of retroposons in the human genome.

A cluster of nine retroposons of four different types in a 6221 base EcoRI DNA fragment was isolated from a human fetal liver genomic library using a human nucleophosmin (B23) cDNA as a probe. These retroposons are: (1) a solitary HERV-K long terminal repeat upstream from; (2) a nucleophosmin processed pseudogene; (3) six Alu repeated sequences interspersed in both directions; and (4) a truncated Kpn repeated sequence integrated by an Alu monomer and the HERV-K long terminal repeat. Sequence analysis shows that the nucleophosmin pseudogene contains a long stretch (135 base-pairs) of homopurine.homopyrimidine (Pur.Pyr) sequence. S1 and P1 nuclease digestion indicated that this sequence was able to adopt a non-B-DNA triplex structure under either acidic or neutral conditions. This finding is the first example of the association of a potential DNA triplex structure with a cluster of retroposons.

Mouse brain localization of the protein kinase C-enhanced phosphatase 1 inhibitor KEPI (kinase C-enhanced PP1 inhibitor).

We recently identified the protein kinase C-enhanced protein phosphatase 1 (PP1) inhibitor KEPI based on its morphine-induced upregulation in striatum. Regulation of protein serine/threonine dephosphorylation by PP1 can modulate important brain signaling pathways. To improve understanding of KEPI's role in the brain, we have developed anti-KEPI sera in rabbits immunized with a hemocyanin conjugate of KEPI residues 66-80, characterized the specificity that this serum provides, mapped the distribution of immunoreactive KEPI (iKEPI) in mouse brain, rat dorsal root ganglia and striatal cultures and documented KEPI binding to PP1 in vitro. Staining is found in apparently neuronal processes and, often less intensely, in neuronal perikarya in primary cultures and in neurons and neuronal elements from a number of brain regions. iKEPI fiber/terminal patterns are relatively densely distributed in striatum, nucleus accumbens, septum, bed nucleus of the stria terminalis, hippocampus, paraventricular thalamus, ventromedial hypothalamus, interpeduncular nucleus, raphe nuclei, nucleus caudalis of the spinal tract of the trigeminal and dorsal horn of the spinal cord. iKEPI-positive cell bodies lie in the nucleus accumbens, striatum, lateral septal nucleus, granular layer of dentate gyrus, interpeduncular nucleus, dorsal root ganglia and cerebellar vermis. These expression patterns point to possible roles for KEPI in regulating protein dephosphorylation by inhibiting PP1 activities in a number of brain pathways likely to use several different neurotransmitters and to participate in a number of brain functions. Dense KEPI immunoreactivity in nucleus accumbens perikarya, combined with evidence for its regulation by opiates, supports possible roles for KEPI in molecular signal transduction pathways important for drug reward and addiction.

27-Hydroxycholesterol contributes to disruptive effects on learning and memory by modulating cholesterol metabolism in the rat brain.

Cholesterol metabolism is important for neuronal function in the central nervous system (CNS). The oxysterol 27-hydroxycholesterol (27-OHC) is a cholesterol metabolite that crosses the blood-brain barrier (BBB) and may be a useful substitutive marker for neurodegenerative diseases. However, the effects of 27-OHC on learning and memory and the underlying mechanisms are unclear. To determine this mechanism, we investigated learning and memory and cholesterol metabolism in rat brain following the injection of various doses of 27-OHC into the caudal vein. We found that 27-OHC increased cholesterol levels and upregulated the expression of liver X receptor-α (LXR-α) and adenosine triphosphate (ATP)-binding cassette transporter protein family member A1 (ABCA1). In addition, 27-OHC decreased the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low-density lipoprotein receptor (LDLR) in rat brain tissues. These findings suggest that 27-OHC may negatively modulate cognitive effects and cholesterol metabolism in the brain.

A rat brain cDNA encoding the neurotransmitter transporter with an unusual structure.

A rat cDNA clone encoding the novel membrane protein of the neurotransmitter transporters family was cloned and sequenced. The cDNA was identified as a transcript of the gene NTT4 of which a partial genomic clone was previously sequenced. Alignment of the amino acid sequence of NTT4 with other members of the neurotransmitter transporter family revealed a marked deviation from the conserved structure of all other members of the family. The largest extracellular loop with a potential glycosylation site was identified between membrane segments 7 and 8. The protein retains the common glycosylated loop between transmembrane helices 3 and 4 in all members of the family. The transcript of NTT4 was found exclusively in the central nervous system and is more abundant in the cerebellum and the cerebral cortex.

Cloning and expression of a glycine transporter from mouse brain.

We have isolated a cDNA clone from a mouse brain library encoding the glycine transporter (GLYT). Xenopus oocytes injected with a synthetic mRNA accumulated [3h]glycine to levels of up to 80-fold above control values. The uptake was specific for glycine and dependent on the presence of Na+ and Cl- in the medium. The cDNA sequence predicts a highly hydrophobic protein of 633 amino acids with 12 potential transmembrane helices. The predicted amino acid sequence has 40-45% identity to the GABA, noradrenaline, serotonin and dopamine transporters. This implies that all of these neurotransmitter transporters may have evolved from a common ancestral gene that diverged into the GABA, glycine and catecholamine subfamilies at nearly the same time.

Characterization of seven processed pseudogenes of nucleophosmin/B23 in the human genome.

Genomic blot analysis revealed that the nucleophosmin/B23 gene belongs to a multigene family that has about 10 copies per haploid human genome. In searching for human nucleophosmin/B23 functional genes, seven processed pseudogenes (NG1-1.6, NG2-6, NG3-3, NG4-5, NG5-4, NG6-4, and NG7-6) were isolated and characterized. Four of them, NG2-6, NG3-3, NG4-5, and NG7-6, contain the sequences corresponding to the full-length cDNA. NG1-1.6 is 5'-truncated, whereas NG5-4 and NG6-5 are 3'-truncated pseudogenes. Of the seven pseudogenes, NG3-3 clone has the longest 5' untranslated sequence, which contains 104 nucleotides upstream of the translation initiation codon (AUG). Two processed pseudogenes (NG2-6 and NG3-3) have different polyadenylation sites from the mRNA, indicating the usage of alternative polyadenylation signals at the 3' sequence.

[Clinical observation of Qi deficiency syndrome in 72 patients with chronic obstructive pulmonary disease treated with yiqi mianyi granule].

Seventy-two patients of chronic obstructive pulmonary disease (COPD) of Qi deficiency syndrome with abnormal immune indices were treated with Yiqi Mianyi Granule (YQMYG) and the efficacy was compared with 30 cases treated with Zhenqi Fuzheng Granule (ZQFZG) for control. Results showed that the marked effective rate of symptomatic improvement of Qi Deficiency in YQMYG group was 65.3%, the total effective rate was 93.1%. 88.6% of the immune indices lower than normal were corrected and 43.7% of them were normalized, while for indices higher than normal the rate were 78.2% and 52.9% respectively. These results suggested that YQMYG could improve the symptom of Qi Deficiency markedly, strengthen the cellular immunity, regulate the disorder of immune function, its therapeutic efficacy was obviously superior to ZQFZG (P < 0.05).

Selective 14-3-3γ induction quenches p-ß-catenin Ser37/Bax-enhanced cell death in cerebral cortical neurons during ischemia.

Ischemia-induced cell death is a major cause of disability or death after stroke. Identifying the key intrinsic protective mechanisms induced by ischemia is critical for the development of effective stroke treatment. Here, we reported that 14-3-3γ was a selective ischemia-inducible survival factor in cerebral cortical neurons reducing cell death by downregulating Bax depend direct 14-3-3γ/p-ß-catenin Ser37 interactions in the nucleus. 14-3-3γ, but not other 14-3-3 isoforms, was upregulated in primary cerebral cortical neurons upon oxygen-glucose deprivation (OGD) as measured by quantitative PCR, western blot and fluorescent immunostaining. The selective induction of 14-3-3γ in cortical neurons by OGD was verified by the in vivo ischemic stroke model. Knocking down 14-3-3γ alone or inhibiting 14-3-3/client interactions was sufficient to induce cell death in normal cultured neurons and exacerbate OGD-induced neuronal death. Ectopic overexpression of 14-3-3γ significantly reduced OGD-induced cell death in cultured neurons. Co-immunoprecipitation and fluorescence resonance energy transfer demonstrated that endogenous 14-3-3γ bound directly to more p-ß-catenin Ser37 but not p-Bad, p-Ask-1, p-p53 and Bax. During OGD, p-ß-catenin Ser37 but not p-ß-catenin Ser45 was increased prominently, which correlated with Bax elevation in cortical neurons. OGD promoted the entry of 14-3-3γ into the nuclei, in correlation with the increase of nuclear p-ß-catenin Ser37 in neurons. Overexpression of 14-3-3γ significantly reduced Bax expression, whereas knockdown of 14-3-3γ increased Bax in cortical neurons. Abolishing ß-catenin phosphorylation at Ser37 (S37A) significantly reduced Bax and cell death in neurons upon OGD. Finally, 14-3-3γ overexpression completely suppressed ß-catenin-enhanced Bax and cell death in neurons upon OGD. Based on these data, we propose that the 14-3-3γ/p-ß-catenin Ser37/Bax axis determines cell survival or death of neurons during ischemia, providing novel therapeutic targets for ischemic stroke as well as other related neurological diseases.

Controlled synthesis of ultra-long AlN nanowires in different densities and in situ investigation of the physical properties of an individual AlN nanowire.

The controlled synthesis of different growth densities of ultra-long AlN nanowires has been successfully realized by nitridation of Al powders for the first time. These AlN nanowires have an average diameter of about 100 nm and their mean length is over 50 µm. All the synthesized ultra-long nanowires are pure single crystalline h-AlN structures with a growth orientation of [0001]. We preferred the self-catalyzing vapor-liquid-solid (VLS) mechanism to illustrate their growth process. Although the sample with the middle growth density (3.2×10(7) per cm2) of AlN nanowire performs the best field emission (FE) properties, the emission uniformity is not good enough for field emission display applications, which may be attributed to their low intrinsic conductivity. Moreover, the electrical transport and FE properties of an individual ultra-long AlN nanowire are further investigated in situ to find the decisive factor responsible for their FE behaviors. An individual AlN nanowire is observed to have a mean 1 nA field of 440 V µm(-1) and 1 µA field of 480 V µm(-1) as well as an average electrical conductivity of about 2.7×10(-4)Ω(-1) cm(-1), which is lower than that of some cathode materials with excellent FE properties. Therefore we come to the conclusion that the electrical conductivity of the AlN nanowire must be improved to a higher level by some effective ways in order to realize their practical FE device applications.

Consequences of cannabinoid and monoaminergic system disruption in a mouse model of autism spectrum disorders.

Autism spectrum disorders (ASDs) are heterogenous neurodevelopmental disorders characterized by impairment in social, communication skills and stereotype behaviors. While autism may be uniquely human, there are behavioral characteristics in ASDs that can be mimicked using animal models. We used the BTBR T+tf/J mice that have been shown to exhibit autism-like behavioral phenotypes to 1). Evaluate cannabinoid-induced behavioral changes using forced swim test (FST) and spontaneous wheel running (SWR) activity and 2). Determine the behavioral and neurochemical changes after the administration of MDMA (20 mg/kg), methamphetamine (10 mg/kg) or MPTP (20 mg/kg). We found that the BTBR mice exhibited an enhanced basal spontaneous locomotor behavior in the SWR test and a reduced depressogenic profile. These responses appeared to be enhanced by the prototypic cannabinoid, Δ(9)-THC. MDMA and MPTP at the doses used did not modify SWR behavior in the BTBR mice whereas MPTP reduced SWR activity in the control CB57BL/6J mice. In the hippocampus, striatum and frontal cortex, the levels of DA and 5-HT and their metabolites were differentially altered in the BTBR and C57BL/6J mice. Our data provides a basis for further studies in evaluating the role of the cannabinoid and monoaminergic systems in the etiology of ASDs.

Increased serum retinol-binding protein-4 levels in pregnant women with and without gestational diabetes mellitus.

OBJECTIVE: Retinol-binding protein 4 (RBP4) is thought to be associated with insulin resistance in humans, while pregnancy is normally characterized by progressive insulin resistance. Gestational diabetes (GDM) occurs when pancreatic beta-cell function is unable to compensate for insulin resistance. This study aimed to determine whether or not serum RBP4 levels are elevated in pregnancy, and to explore the relationship between RBP4 levels and insulin resistance during pregnancy. METHODS: Serum RBP4 was measured at median gestational week 26 in 121 pregnant women, including 63 with GDM (GDM group) and 58 normal, glucose-tolerant pregnant women (P-NGT group), as well as 65 non-pregnant normal, glucose-tolerant women (NP-NGT group). Multiple stepwise regression analysis was used to explore the independent factors of RBP4. RESULTS: Serum RBP4 levels in the P-NGT and GDM groups were significantly higher than in the NP-NGT group (34.50±9.80 mg/L and 41.64±12.21 mg/L vs 30.64±9.46 mg/L, respectively; P<0.05) after adjusting for age, body mass index (BMI) and blood pressure. Furthermore, RBP4 levels were much higher in the GDM vs P-NGT group. Spearman's correlation analysis showed that serum RBP4 levels were positively correlated with triglycerides (TG), fasting plasma glucose, postprandial 2h plasma glucose and HOMA-IR in pregnancy. Of these, TG and HOMA-IR (r(2)=0.312) were independent factors of serum RBP4. CONCLUSION: Serum RBP4 levels are significantly increased in pregnancy, independent of age and BMI, and are also considerably higher in pregnant women with GDM than in those with normal glucose tolerance. In addition, serum RBP4 levels appear to be a valuable marker of insulin resistance and dysfunctional lipid metabolism in pregnancy.