[Effect of different concentrations of ammonium chloride on expression of hypoxia-inducible factor-1α in Chang liver cells].

Objective: To investigate the effect of treatment with different concentrations of ammonium chloride (NH4Cl) on the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in Chang liver cells. Methods: Normal Chang liver cells were cultured and treated continuously with different concentrations of NH4Cl (1.25, 2.5, and 5 mmol/L). The Chang liver cells cultured normally were used as controls. RNA and protein were extracted at the 5th, 10th, and 15th generations. Quantitative real-time PCR, immunohistochemistry, and Western blot were used to measure the expression of HIF-1α and VEGF. Results: Quantitative real-time PCR showed that compared with the control group, the NH4Cl treatment group showed significant increases in the mRNA expression of HIF-1α and VEGF across the 5th, 10th, and 15th generations (F = 90976.659/1300.218/1896.800 and 41825.754/2381.321/2591.954, all P < 0.05). The results of immunohistochemistry showed that compared with the control group, the NH4Cl treatment group showed significant increases in the protein expression of HIF-1α and VEGF across the 5th, 10th, and 15th generations (F = 376.709/1615.358/1350.120 and 904.789/5105.186/8644.498, all P < 0.05). As was shown by the results of Western blot, compared with the control group, the NH4Cl treatment group showed significant increases in the protein expression of HIF-1α and VEGF across the 5th, 10th, and 15th generations (F = 228.499/6051.974/183.219 and 5549.429/40187.665/120982.183, all P < 0.05). Conclusion: Ammonia can increase the expression of HIF-1α and its downstream gene VEGF in Chang liver cells and cause the phenomenon of pseudohypoxemia.

[Effects of ß-blockers in patients with septic shock: a meta analysis].

OBJECTIVE: To evaluate the effect of ß-blockers in patients with septic shock. METHODS: PubMed, EMBASE, Cochrane central registration of controlled trials, CNKI and Wanfang Data were searched to identify relevant studies from inception to October 2015.Statistical analysis was performed using STATA 12.0.The random effects model was used due to wide clinical variability across the trials. RESULTS: After application of the inclusion criteria, 7 trials with 392 patients were included, involving 3 randomized controlled trials (RCT) and 4 quasi-experiments.The results of the meta-analysis for the quasi-experiments showed that compared with baseline, heart rates (standardized mean difference (SMD)=-2.51, 95%CI: -4.32--0.70, P=0.007) and lactate levels (SMD=-0.34, 95%CI: -0.67--0.02, P=0.039) significantly decreased, while no significant differences were seen for mean arterial pressure (SMD=0.01, 95%CI: -0.42-0.44, P=0.969), cardiac index (SMD=-0.35, 95%CI: -1.15-0.44, P=0.385) or norepinephrine requirements (SMD=-0.06, 95%CI: -0.38-0.27, P=0.726) after 24-hour therapy. Among randomized controlled trials, ß-blockers, compared with standard care, was associated with reductions in heart rates (P<0.001) , 28-day mortality (RR=0.60, 95%CI: 0.48-0.75, P<0.001) and troponin I levels (P<0.001). While no differences were found between the two groups in other hemodynamic and cardiac function variables, such as mean arterial pressure, cardiac index or stroke volume index (P>0.05). CONCLUSIONS: The currently available evidence indicates that the use of ß-blockers is associated with a significant decrease in heart rate, troponin I levels and 28-day mortality in patients with septic shock, while mean arterial pressure, cardiac index and stroke volume index might remain unchanged.Large scale, muti-center RCTs need to be carried out to confirm the effects of ß-blockers in patients with septic shock.

Clinical effects of thermotherapy in combination with intracavitary infusion of traditional Chinese medicine in the treatment of malignant pleural effusion.

Malignant fluid, a commonly seen tumor associated complication, mainly includes peritoneal effusion, malignant pleural effusion and pericardial effusion. It can produce huge negative influence on the quality of life of patients and even lead to death. Treatment of malignant effusion is one of the effective measures for improving life expectancy of patients. To evaluate the effect of thermotherapy in combination with intracavitary infusion of Kangai injection in treating malignant pleural effusion, 195 patients who received treatment from April 2010 to October 2014 in the First Affiliated Hospital of Zhengzhou University were selected and divided into an observation group and two control groups (group A and B). The observation group was treated by thermotherapy in combination with intracavitary infusion of kangai injection. Control group A was treated by intracavitary infusion of kangai injection and control group B was treated by hyperthermal perfusion in combination with intracavity chemotherapy. Clinical effects, quality of life, treatment safety and untoward reactions were compared between the groups. It was found that differences of WBC, RBC and PLT levels before and after treatment had no statistical significance comparisons within group and comparisons between groups (P>0.05); hepatic and renal functions of the groups had no remarkable difference before or after treatment (P>0.05). The clinical effect of the observation group was superior to that of control groups A and B (P less than 0.05); the Karnofsky performance status (KPS) score of the observation group was much higher than that of control groups A and B (79.34±10.58 vs 71.11±9.64), but the difference of the ZPS score between groups had no statistical significance (P>0.05). It can be concluded that thermotherapy in combination with intracavitary infusion of traditional Chinese medicine can be safely applied as it has positive effects and remarkably improves quality of life, therefore it is clinically worth promoting.

Vector-mediated expression of interferon gamma inhibits replication of hepatitis B virus in vitro.

Despite the existence of efficient vaccines against hepatitis B virus (HBV) infections, these still represent a serious threat to human health worldwide. Acute HBV infections often become chronic, marked by liver cirrhosis and hepatocellular carcinoma. Promising results with interferons alpha or gamma (IFN-α, γ) or nucleoside/nucleotide analogs in inhibiting HBV replication in vitro have led to therapeutic applications to chronic HBV patients, however, their results so far have not been satisfactory. The treatments were either not effective in all patients or had adverse effects. Certain progress was expected from expression of interferons targeted to liver by adenovirus vectors, however, this approach turned out to be limited by undesired expression of toxic viral genes and high production costs. Therefore, in this study, we attempted to inhibit HBV replication in HepG2.2.15 cells by human IFN-γ expressed through a non-viral vector, an eukaryotic plasmid. The results demonstrated that IFN-γ, targeted to HBV-replicating cells, significantly inhibited the virus growth without inducing apoptosis and indicated that local expression of this kind of cytokine may be a promising strategy of gene therapy.

Effects of CYP3A5 and CYP2D6 genetic polymorphism on the pharmacokinetics of diltiazem and its metabolites in Chinese subjects.

PURPOSE: To assess the possibility of using CYP2D6 10 +/- CYP3A5*3 as biomarkers to predict the pharmacokinetics of diltiazem and its two metabolites among healthy Chinese subjects. METHODS 41 healthy Chinese were genotyped for CYP3A5 3 and CYP2D6 10, and then received a single oral dose of diltiazem hydrochloride capsules (300 mg). Multiple blood samples were collected over 48 h, and the plasma concentrations of diltiazem, N-desmethyl diltiazem and desacetyl diltiazem were determined by HPLC-MS/MS. The relationships between the genotypes and pharmacokinetics were investigated. RESULTS: The pharmacokinetics of diltiazem, N-desmethyl diltiazem were not significantly affected by both CYP3A5 3 and CYP2D6*10 alleles. However, the systemic exposure of the pharmacologyically active metabolites, desacetyl diltiazem, was 2-fold higher in CYP2D6 10/10 genotype carriers than in 1/10 or 1/1 ones (AUC(o-inf) of CYP2D6 1/1, 1/10 and 10/10 are 398.2 +/- 162.9, 371,0 69.2 and 726.2 +/- 468.1 respectively, p <0.05). CONCLUSIONS: Two of the most frequent alleles, CYP3A5 3 and CYP2D6 10, among Chinese do not have major impacts on the disposition of diltiazem and N-desmethyl diltiazem. However, the desacetyl diltiazem showed 2-fold accumulation in individuals with CYP2D6 10/10 genotype. Despite this, the effect of genotype of CYP2D6 on clinical outcome of diltiazem treatment is expected to be limited.

Study of the OPRM1 A118G genetic polymorphism associated with postoperative nausea and vomiting induced by fentanyl intravenous analgesia.

BACKGROUND: Genetic polymorphisms of the µ-opioid receptor gene OPRM1 A118G have been shown to influence opioid efficacy. The association of the OPRM1 A118G genetic polymorphism with side effects, such as nausea and vomiting, caused by opioids during analgesia has not been well-represented by the literature . This study aimed to investigate whether the genetic polymorphism of OPRM1 A118G contributed to the variability in nausea and vomiting during fentanyl analgesia in patients undergoing total abdominal hysterectomy or myomectomy. METHODS: One hundred sixty-five women, of Han nationality, aged 20-50 yrs, of ASA I or II, and scheduled for elective total abdominal hysterectomy or myomectomy under general anesthesia were enrolled. Intravenous fentanyl, patient-controlled analgesia was provided postoperatively for pain control. The presence and scores of postoperative nausea and vomiting for 24 hours were recorded and measured using rating scales. Pain was measured with a visual analog scale, and fentanyl consumption over 24 hours was recorded, as well. Genotyping of the A118G allele was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and patients were divided into three groups according to their genotype. RESULTS: The frequency of the A118G allele was 32.4% for the patients in this study. Patients homozygous for 118G required more fentanyl to achieve adequate pain relief compared with the other two patient groups (patients homozygous for 118A and heterozygous). However, there were no statistically significant differences among the frequencies and scores of nausea and vomiting. CONCLUSION: OPRM1 A118G has no effect on the individual variation of postoperative nausea and vomiting, the side effects of fentanyl analgesia, in Chinese women undergoing gynecologic surgery.

Association of human micro-opioid receptor gene polymorphism A118G with fentanyl analgesia consumption in Chinese gynaecological patients.

One hundred and seventy-four Chinese gynaecology patients were studied for the impact of A118G polymorphism in the micro-opioid receptor gene (OPRM1) on pain sensitivity and postoperative fentanyl consumption. Pre-operatively, the pain threshold and pain tolerance threshold were measured using electrical stimulation. A118G polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Intravenous fentanyl patient-controlled analgesia provided postoperative pain management, assessed using a visual analogue scale and fentanyl consumed in the first 24 h after surgery was noted. We found the prevalence of G118 allele was 31.3%. The A118G polymorphism had a gene-dose-dependent effect on electrical pain tolerance threshold. Fentanyl consumption was also significantly different in patients with different OPRM1 genotypes (homozygotes for 118G consumed more than did heterozygotes or homozygotes for 118A). Fentanyl consumption increased in accordance with the number of 118G alleles. We conclude that OPRM1 gene analysis may help predict individual opioid sensitivity and so optimise postoperative pain control.