The value of dual time-point fluorine-18 fluorodeoxyglucose PET/computed tomography imaging in predicting lymph node metastasis in non-small cell lung cancer patients.

OBJECTIVE: The purpose of this study was to analyze the correlation between specified dual time-point fluorine-18 fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) imaging parameters and pathological characteristics in non-small cell lung cancer (NSCLC) patients. METHODS: This study retrospectively analyzed 47 patients with NSCLC. All patients underwent dual time-point 18F-FDG PET/CT imaging. We obtained the metabolic parameters, standardized uptake value (SUV) maximum, SUVmean, delayed standardized uptake value (DSUV) maximum, DSUVmean, delay index standardized uptake value (DISUV) maximum, and DISUVmean, of the primary tumor. The tumor size was measured by CT. All lymph nodes had a definite pathological diagnosis. We next evaluated the status of the lymph node metastases (LNM) and the correlations between metabolic parameters and clinical characteristics. Receiver operating characteristic curves were drawn for the prediction of LNM. RESULTS: We found that the DSUVmax, DISUVmax, DSUVmean, and tumor size were significantly related to LNM (P = 0.036, 0.009, and 0.049, respectively). Multivariate analysis revealed that tumor size and DISUVmax were independent risk factors for LNM in lung cancer patients. According to the receiver operating characteristic curve analysis, the optimal cutoff values for DISUVmax and tumor size were 0.33 and 2.8 cm, respectively. When these two parameters were combined, the area under the curve for predicting LNM in NSCLC was 0.768, and the sensitivity was 95.7% for predicting LNM in lung cancer patients. We further allocated the patients to three groups: the high-risk group (tumor size ≥ 2.8 cm, DISUVmax ≥ 0.33), the moderate-risk group (tumor size ≥ 2.8 cm, DISUVmax < 0.33, or tumor size < 2.8 cm, DISUVmax ≥ 0.33), and the low-risk group (tumor size < 2.8 cm, DISUVmax < 0.33). The rates of LNM were 70, 50, and 0%, respectively. CONCLUSION: Tumor size and DISUVmax are risk factors for predicting LNM, and they are more useful in combination. Compared with standard PET/CT imaging, dual time-point PET/CT imaging has added value in predicting LNM in NSCLC patients.

The effect of lycopene on cytochrome P450 isoenzymes and P-glycoprotein by using human liver microsomes and Caco-2 cell monolayer model.

Lycopene is widely used as a dietary supplement. However, the effects of lycopene on cytochrome P450 (CYP) enzymes or P-glycoprotein (P-gp) are not comprehensive. The present study was performed to investigate the effects of lycopene on the CYP enzymes and P-gp activity. A cocktail method was used to evaluate the activities of CYP3A4, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. Caco-2 cell monolayer model was carried out to assay lycopene on P-gp activity. The results indicated that lycopene had a moderate inhibitory effect on CYP2E1, with IC50 value of 43.65 µM, whereas no inhibitory effects on CYP3A4, CYP2C19, CYP2D6 and CYP2E1, with IC50 values all over 100 µM. In addition, lycopene showed almost no inhibitory effect on rhodamine-123 efflux and uptake (p > .05), indicated no effects on P-gp activity. In conclusion, there should be required attention when lycopene are coadministered with other drugs that are metabolised by CYP2E1.

Protective effect and mechanism of ginsenoside Rg1 on carbon tetrachloride­induced acute liver injury.

Liver injury is a common pathological state in various types of liver disease; severe or persistent liver damage is the basis of hepatic failure. Ginsenoside Rg1 (Rg1), one of the primary active ingredients of ginseng, has been reported to reduce concanalin A­induced hepatitis and protect against lipopolysaccharide­ and galactosamine­induced liver injury. However, the underlying protective mechanism of Rg1 in acute liver injury remains unclear. In the present study, a carbon tetrachloride (CCl4)­induced acute liver injury model was established, and the protective effect of Rg1 on CCl4­induced acute liver injury was demonstrated in cell culture and animal experimental systems. Further investigation of the mechanisms demonstrated that pretreatment with Rg1 reduced elevated levels of alanine aminotransferase and aspartate aminotransferase, enhanced the antioxidant activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) content. Experiments in vitro demonstrated that Rg1 decreased p65 expression and inhibited nuclear factor (NF)­κB activity. In addition to the effect of Rg1, an NF­κB inhibitor promoted cell survival, enhanced SOD activity and reduced MDA level. It was observed through in vivo experiments that pretreatment with Rg1 inhibited NF­κB expression and activity in Kupffer cells and reduced the serum levels of tumor necrosis factor­α and interleukin­6. In conclusion, the results of the present study indicated that pretreatment with Rg1 may rescue CCl4­induced acute liver injury in vivo and in vitro through inhibition of NF­κB activity, to restore the anti­oxidative defense system and down­regulate pro­inflammatory signaling pathways. The present observations provide a theoretical foundation for the clinical application of Rg1 therapy in acute liver injury.

Antifreeze poisoning: A case report.

The current study reported the case of a 35-year-old male that presented with antifreeze poisoning. The clinical manifestations, laboratory investigations and treatments were analyzed, and the obtained results were compared with those in previous reports. Subsequent to consuming antifreeze, the patient mainly presented nausea and agitation, without disturbance of consciousness. Laboratory investigations indicated severe metabolic acidosis, renal dysfunction and hyperkalemia. The patient underwent hemodialysis and his condition was significantly improved on the day of admission. Renal function gradually deteriorated, but was eventually improved due to treatment, including hemodialysis, mannitol for catharsis, furosemide for diuresis, Xuebijing for the removal of blood stasis and detoxication, and reduced glutathione for the protection of major organs. The patient was discharged 1 month after hospital admission. In conclusion, the significance and clinical manifestations of antifreeze poisoning should be identified in clinical practice, and active hemodialysis should be provided. The aim of the current study was to summarize the clinical manifestations and treatments of patients with antifreeze poisoning, and to advance the recognition of antifreeze poisoning.

Severe adverse reactions caused by omeprazole: A case report.

A 61-year-old female patient was admitted to hospital following development of a whole-body rash for 10 days, diarrhea for 7 days, and unconsciousness and oliguria for 1 day. The patient had developed stomach discomfort following the oral administration of non-steroidal anti-inflammatory drugs, the exact nature of which was unknown, for the treatment of arthritic pain for >1 month. The patient was then prescribed omeprazole enteric-coated tablets (20 mg twice daily) for treatment of this symptom. However, the patient developed a whole-body rash 7 days after administering omeprazole, 10 days prior to admission. This symptom was followed by severe diarrhea with nausea and vomiting after 10 days, then shock. The shock occurred after administering omeprazole for 16 days. The patient developed a whole body rash 7 days after administering omeprazole, then 3 days later (after administering omeprazole for 10 days) severe diarrhea with nausea and vomiting occurred. The shock remained until administering omeprazole on the 16th day, with severe diarrhea with nausea and vomiting occurring 6 days later. The patient's condition did not improve following treatment for allergies, low blood pressure and oliguria in the Intensive Care Unit (ICU) department at Suzhou Municipal Hospital. For further diagnosis and treatment, the patient was admitted to the ICU department of The First Affiliated Hospital of Bengbu Medical College and was given a fluid infusion, antibiotics and phlegm-reducing treatment, a plasma infusion, blood filtration, and anti-diarrheal and anti-allergy treatment. The patient's vital signs were stable, with a normal temperature and hemogram results, and improved kidney function and deflorescence. Genetic screening revealed that the patient poorly metabolized omeprazole. Therefore, severe adverse reactions (allergic shock, rash and diarrhea) experienced by the patient were caused by the accumulation of omeprazole metabolites resulting from its slow metabolism in vivo.

The Effect of Vinpocetine on Human Cytochrome P450 Isoenzymes by Using a Cocktail Method.

Vinpocetine is a derivative of the alkaloid vincamine, which had been prescribed for chronic cerebral vascular ischemia and acute ischemic stroke or used as a dietary supplement for its several different mechanisms of biological activities. However, information on the cytochrome P450 (CYP) enzyme-mediated drug metabolism has not been previously studied. The present study was performed to investigate the effects of vinpocetine on CYPs activity, and cocktail method was used, respectively. To evaluate the effects of vinpocetine on the activity of human CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, human liver microsomes were utilized to incubate with the mixed CYPs probe substrates and the target components. The results indicate that vinpocetine exhibited weak inhibitory effect on the CYP2C9, where the IC50 value is 68.96 µM, whereas the IC50 values for CYP3A4, CYP2C19, CYP2D6, and CYP2E1 were all over range of 100 µM, which showed that vinpocetine had no apparent inhibitory effects on these CYPs. In conclusion, the results indicated that drugs metabolized by CYP2C9 coadministrated with vinpocetine may require attention or dose adjustment.

Ginsenoside Rg1 attenuates invasion and migration by inhibiting transforming growth factor-ß1-induced epithelial to mesenchymal transition in HepG2 cells.

Ginseng has become one of the most commonly used alternative herbal medicines and its active component, ginsenoside Rg1, possesses known pharmacological effects, including anticancer properties. However, the effects of ginsenoside Rg1 on metastasis have not been investigated. The present study demonstrated that ginsenoside Rg1 was able to suppress transforming growth factor­ß1 (TGF­ß1)­induced invasion and migration in HepG2 liver cancer cells. This suppression was associated with the inhibition of TGF­ß1­induced epithelial to mesenchymal transition (EMT). Furthermore, TGF­ß1 induced HepG2 cells to undergo EMT and significantly promoted cell invasion and migration. When cells were pretreated with ginsenoside Rg1 for 24 h and subsequently exposed to TGF­ß1 for 24 h, the results demonstrated that ginsenoside Rg1 inhibited the initiation of TGF­ß1­induced EMT. In addition, HepG2 cells exhibited a mesenchymal phenotype when exposed to TGF­ß1, but when exposed to ginsenoside Rg1 this effect was reversed and the cells exhibited a classical epithelial morphology. Ginsenoside Rg1 also increased the expression of the epithelial phenotype marker E­cadherin and repressed the expression of the mesenchymal phenotype marker vimentin. In conclusion, the results of the present study suggest that ginsenoside Rg1 may suppress liver cancer invasion and migration in vitro through inhibiting TGF­ß1­induced EMT.

Suppression of PMA-induced tumor cell invasion and migration by ginsenoside Rg1 via the inhibition of NF-κB-dependent MMP-9 expression.

Ginseng has become one of the most commonly used alternative herbal medicines, and its active component, ginsenoside Rg1 has known pharmacological effects, including anticancer properties. However, the effects of ginsenoside Rg1 on metastasis have yet to be investigated. In this study, we demonstrated the ability of ginsenoside Rg1 to suppress phorbol myristate acetate (PMA)-induced invasion and migration in MCF-7 breast cancer cells. MCF-7 cells were treated with ginsenoside Rg1 and incubated with or without PMA. The protein and mRNA expression of MMP-9 and MMP-2 was analyzed using Transwell and wound­healing assays and western blotting. The results showed that suppression was associated with the reduced secretion of MMP-9, a key metastatic enzyme. MMP-9 levels were regulated transcriptionally and correlated with the suppression of NF-κB phosphorylation and DNA binding activity. Conversely, ginsenoside Rg1 did not affect MMP-2 mRNA and TIMP-1 mRNA levels, or the activation of AP-1, suggesting a specificity of pathway inhibition. Inhibition of NF­κB activation by p65 small­interfering RNA (siRNA) was shown to suppress PMA-induced cell invasion and migration. The siRNA studies also showed that PMA-induced MMP-9 expression is NF-κB-dependent. The results suggested that the anticancer properties of ginsenoside Rg1 may derive from its ability to inhibit invasion and migration, and that these processes are regulated in breast cancer cells through the NF-κB­mediated regulation of MMP-9 expression.