The Effect of Dihydromyricetin on the Pharmacokinetics of Fluconazole in Sprague-Dawley Rat Plasma, Based on High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Background: The synergistic effect of dihydromyricetin (DHM) and fluconazole (FLC) can improve the killing effect of FLC-resistant Candida albicans in vitro and in vivo. However, it is not clear whether DHM affects the pharmacokinetic characteristics of FLC. Methods: In this study, 12 Sprague-Dawley (SD) rats were randomly divided into two groups as follows: (1) an FLC group in which rats were administered FLC only (42 mg/kg orally); (2) an FLC with the combined administration of DHM group, in which rats received an equivalent FLC dose immediately following the administration of DHM (100 mg/kg). Blood samples were collected from the ocular choroid vein of rats and converted into plasma. The concentrations of FLC in the rat plasma were then determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the related pharmacokinetic parameters were analysed. The initial mobile phase included 0.1% acetonitrile and water with gradient elution. Multiple reaction monitoring modes of m/z 307.2→220.1 for FLC, and m/z 237.1→194.2 for carbamazepine, were utilised to conduct quantitative analysis. Results: The calibration curve of FLC in rat plasma demonstrated good linearity in the range of 0.1-30 µg/mL (r > 0.99), and the lower limit of quantification was 0.1 µg/mL. Moreover, the intra- and inter-day precision relative standard deviation of FLC was less than 9.09% and 6.51%, respectively. There were no significant differences in the pharmacokinetic parameters between the two groups. Conclusion: The results showed that DHM administration did not significantly alter FLC pharmacokinetics in SD rat plasma.

Graft-versus-host disease-like erythroderma: a sign of recurrent thymoma: A case report.

RATIONALE: Thymomas are associated with numerous autoimmune disorders, such as myasthenia gravis (MG), pure red cell aplasia (PRCA), and systemic lupus erythematosus (SLE). However, graft-versus-host disease (GVHD)-like erythroderma is a relatively uncommon paraneoplastic disorder associated with thymomas and signifies a poor prognosis. PATIENT CONCERNS: A 35-year-old woman with medical history significant for stage IVa type AB thymoma presented with patchy erythema over face, trunk, and extremities that failed to respond to topical steroids. DIAGNOSIS: A contrast-enhanced computerized tomography (CECT) scan of the chest demonstrated tumors in the right mediastinum and right pleura. Percutaneous right mediastinal pleural biopsy confirmed recurrent thymoma (WHO type B3, Masaoka stage IVb). Histopathologic examination of her skin lesions revealed GVHD-like erythroderma. INTERVENTIONS: The patient received chemotherapy and local thoracic radiotherapy, as well as corticosteroids. OUTCOMES: The eruptions gradually subsided with hyperpigmentation; however the patient eventually died of multiple organ failure. LESSONS: GVHD-like erythroderma is an uncommon paraneoplastic disorder associated with thymomas. Though its pathogenesis still needs further research, prompt diagnosis and appropriate treatment can improve survival rate in patients.

Polymorphisms of co-inhibitory molecules (CTLA-4/PD-1/PD-L1) and the risk of non-small cell lung cancer in a Chinese population.

Lung cancer is a leading cause of cancer-related death in China, with non-small cell lung cancer (NSCLC) comprises the most common form. Co-inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1) and its ligand PD-L1, play a key roles in the physiopathological process of tumorigenesis. To investigate whether genetic variations of co-inhibitory molecules are associated with the risk of NSCLC, we analyzed polymorphisms of CTLA-4 (-318, +49), PD-1 (PD-1.1, PD-1.3, PD-1.5, PD-1.9) and PD-L1 (+8293) in a cohort of 528 NSCLC subjects and 600 healthy controls. By restriction fragment length polymorphism (RFLP) method, we found that the distributions of the CTLA-4 and PD-1 gene polymorphisms were similar between NSCLC patients and healthy controls. However, for the PD-L1 8923 A/C polymorphism, frequencies of the AC genotype and C-allele were significantly higher in NSCLC patients than in healthy controls (odds ratio [OR] =1.55; 95% confidence interval [CI] 1.13-2.13; P=0.006; OR=1.52; 95% CI 1.14-2.04; P=0.004, respectively). Stratification analysis revealed that prevalence of the 8923C allele was significantly increased in NSCLC patients who smoke compared to those non-smoking patients (OR=1.51; 95% CI 1.00-2.28; P<0.05). Moreover, NSCLC patients carrying the C-allele had higher risk of regional lymph node metastasis than those carrying the A-allele (OR=5.65; 95% CI 2.45~13.03; P<0.001). These data suggest that PD-L1+8293A>C polymorphism may play a role in the development and progression of NSCLC.

LTA + 252A > G polymorphism is associated with risk of nasal NK/T-cell lymphoma in a Chinese population: a case-control study.

BACKGROUND: Nasal NK/T-cell lymphoma is a rare type of lymphoma in Caucasian individuals, but is relatively common in Asian populations. Genetic variants in immune and inflammatory response genes may thus be associated with the risk of developing lymphoma. Here, we investigated the association between immuno-modulatory gene polymorphisms and risk for nasal NK/T-cell lymphoma in a Chinese population. METHODS: Analysis of 12 single nucleotide polymorphisms (SNPs) in IL-10, TNF-α, lymphotoxin-α (LTA), and CTLA-4 genes was performed for 125 patients with NK/T-cell lymphoma and 300 healthy controls by PCR-ligase detection reactions. RESULTS: The LTA +252 GA + AA genotypes were associated with increased risk for NK/T-cell lymphoma (OR = 2.96, 95 % CI = 1.42-6.19, P = 0.004 for GA + AA genotype). Haplotype C-G-G-A (TNF-α -857, -308, -238 and LTA +252) also conferred an increased risk (OR = 1.52, 95% CI = 1.14-2.06, P = 0.005). Additionally, the LTA +252 GA + AA genotype was associated with an even higher risk in populations positive for Epstein-Barr virus (OR = 5.20, 95% CI = 1.22-23.41, P = 0.03 for the GA + AA genotype). CONCLUSIONS: Our data suggest that the LTA +252 A > G polymorphism is associated with the risk of developing NK/T-cell lymphoma, especially for Epstein-Barr virus-positive NK/T-cell lymphoma in the Chinese population.

Interleukin 17A polymorphism elevates gene expression and is associated with increased risk of nonsmall cell lung cancer.

Interleukin 17 (IL-17), also known as IL-17A, is a proinflammatory cytokine and plays critical roles in tumor immunity. Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancers. The aim of this study was to investigate the correlation between IL-17A genetic polymorphisms and susceptibility to NSCLC. Two single nucleotide polymorphisms (SNPs) in IL-17A gene, rs3819024A/G and rs8193037G/A, were detected in 322 NSCLC patients and 366 healthy donors. Data revealed that prevalence of IL-17A rs8193037GA and AA genotypes were significantly higher in the patients than in controls (odds ratio [OR]: 2.20, 95% confidence interval [CI]: 1.53-3.16, p<0.001; and OR: 3.19, 95% CI: 1.42-7.15, p=0.003). Stratification analyses showed that rs8193037A allele had significantly higher percentage in adenocarcinoma than in squamous cell carcinoma (OR: 1.72, 95% CI: 1.12-2.64, p=0.013). When examining the possible function of the SNPs, we found that in vitro stimulated peripheral blood mononuclear cells from subjects possessing rs8193037A allele produced significantly more IL-17 than those with the GG genotype, and this phenomenon could be observed in both controls and the NSCLC patients. These data indicate IL-17A polymorphism is associated with increased risk of NSCLC probably by elevating gene expression.

Chemical constituents of Trachelospermum jasminoides.

Ten compounds, comprising a new C(8) normonoterpenoid glycoside, trachelinoside (1), structurally as 4-(2-O-beta-D-glucopyranosyl)-hydroxyethyl-5,5-dimethyldihydrofuran-2(3H)-one, together with nine known compounds, were isolated from the 85% ethanol extract of the vines and leaves of Trachelospermum jasminoides (Lindl.) Lem.

[Study on the flavonoids constituents of Trachelospermum jasminoides].

OBJECTIVE: To study the flavonoids constituents of Trachelospemum jasminoides. METHODS: The compounds were separated and purified by column chromatography with silica gel, and identified by IR, MS, NMR and 2D-NMR. RESULTS: Six flavonoids were identified as apigenin (I), apigenin 7-O-beta-glucoside (II), apigenin 7-O-beta-neospheroside (III), luteoloside (IV), narngin (V) 6,8-di-C-glucopyanosylapigenin (VI), respectively. CONCLUSION: Compounds V and VI are isolated from this plant for the first time.

[Comparison of treatment efficacy of the second and the third generations of chemoradiotherapy regimens containing platinum on advanced non-small cell lung cancer].

BACKGROUND & OBJECTIVE: Platinum-based chemotherapy regimens are better than other regimens when treating patients with advanced non-small cell lung cancer (NSCLC). The third generation of platinum-based regimens {NP [Navelbine (NVB), cisplatin (DDP)], TP (Taxol, DDP), GP (Gemzar, DDP)} is better than the second generation {MVP [mitomycin (MMC), desacetylvinblastin amide (VDS), DDP], MIP [MMC, ifosfamide (IFO), DDP], EP [etopside (VP-16), DDP], VDS+DDP}. This study was to compare the efficacy between the second and the third generations of platinum-based regimens combined with radiotherapy on advanced non-small cell lung cancer (NSCLC). METHODS: From Jul. 1999 to Dec. 2001, 47 pathologically confirmed advanced NSCLC patients received chemoradiotherapy: 24 received the second generation of platinum-based regimens, 23 received the third generation; all patients received routine external irradiation of (60)Co (65-76 Gy). Characteristics of the patients were comparable. Kaplan-Meier analysis was used to evaluate survival rates, and log-rank test to study differences between the 2 groups. RESULTS: The objective response rates were 41.7% in the second generation group, and 56.5% in the third generation group (Chi (2)=0.53, P=0.47). The median time to progression and median survival time were significantly longer in the third generation group than in the second generation group (12.6 months vs. 6.0 months, Chi(2)=6.93, P=0.01; 14.0 months vs. 9.0 months, Z=-2.17, P=0.03). The 1-, and 2-year survival rates were significantly higher in the third generation group than in the second generation group (56.3% vs. 30.7%, 15.6% vs. 0%, Chi(2)=6.59, P=0.01). The major adverse events were leukocytopenia, nausea and vomiting, radiation-induced esophagitis and pneumonia, which were tolerable. CONCLUSIONS: The third generation of platinum-based regimens in combination with radiotherapy for advanced non-small lung cancer may be more advantageous over the second generation of platinum-based regimens in prolonging survival of advanced NSCLC patients, which would be worth being studied further.