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Irinotecan-induced hepatotoxicity can cause severe clinical complications in patients; however, the underlying mechanism and factors affecting hepatotoxicity have rarely been investigated. In this cross-sectional study, we screened all clinical, demographic, medication, and genetic variables among 126 patients receiving irinotecan and explored potential associations with the incidence and time to onset of irinotecan-induced hepatotoxicity. Approximately 38.9% of the patients suffered from hepatotoxicity after irinotecan administration. The presence of cardiovascular diseases increases the incidence of hepatotoxicity ≈2.9-fold and doubles the hazard of time to hepatotoxicity. Patients with liver metastasis had a4-fold higher risk of hepatotoxicity and a 3.5-fold increased hazard of time to hepatotoxicity compared to those without liver metastasis. Patients who took cytochrome P450 (CYP) 3A inducers had a 4.4-fold increased incidence of hepatotoxicity, and furthermore, concomitant use of platinum-based antineoplastics revealed 4.2 times the hazard of time to hepatotoxicity compared to those receiving antimetabolites. The cumulative dose of irinotecan (5-9 cycles) increased hepatotoxicity by 8.5 times. However, the genotypes and phenotypes of UGT1A1*28/*6 failed to be predictive factors of hepatotoxicity. The findings of this study suggest that irinotecan-induced hepatotoxicity is not directly associated with genetic variables but is mostly related to concomitant use of CYP3A4 inducers and platinum, as well as the presence of liver metastasis and cardiovascular disease. Thus, close monitoring of liver function is recommended, especially in patients with liver impairment or using CYP3A inducers and platinum antineoplastic drugs, which may be the best way to prevent hepatotoxicity.

Most patients experience severe hematological toxicity during treatment with gemcitabine; thus, preventing such toxicity would improve the treatment effects and patient quality of life. We analyzed 13 polymorphisms in the transporters, metabolizing enzymes, targets, and genes involved in DNA damage and the folate pathway among 132 patients treated with gemcitabine and studied their association with the severity of the hematological toxicities. Single-locus analysis showed that the single-nucleotide polymorphisms (SNPs) RRM1 rs12806698 and rs11031918 and DCTD rs7663494 were significantly associated with severe neutropenia, hENT1 rs760370 and hCNT3 rs7867504 and rs4877831 were associated with severe leukopenia, CDA rs2072671, DCTD rs7663494, and WEE1 rs3910384 were associated with severe anemia, and MTHFR rs1801133 was associated with severe thrombocytopenia after stringent Bonferroni correction (P < .0038). The gene-gene interaction analysis identified the overall best models, including a 2-way interaction model (hCNT3 rs7867504 and dCK rs12648166) for severe leukopenia (P = .0022) and a 3-locus model (CDA rs207671, DCTD rs7663494, and WEE1 rs3910384) for severe anemia with a strong synergistic effect (P = .0001). The association with hematological toxicity was further strengthened by the results of a haplotype analysis, in which the homozygous genotype combination of rs3910384 CC, rs2072671 AA, rs12648166 GG, rs7867504 CC, and rs7663494 TT conferred high genetic susceptibility to severe thrombocytopenia. Our results suggest that the gene-gene interaction of gemcitabine metabolic pathway genes and WEE1 contributes to susceptibility to gemcitabine-induced hematological toxicity. Moreover, we propose a promising data-mining analysis approach (generalized multifactor dimensionality reduction) to detect and characterize gene-gene interactions.

Prior pulmonary tuberculosis (PTB) on chest X-ray (CXR) was commonly found in infertile patients receiving examinations beforeWe conducted a retrospective cohort study of 14,254 infertile patients who had received IVF-ET at Peking University Third Hospital in 2017. Prior PTB was defined as the presence of signs suggestive of old or inactive PTB on CXR, with or without a clinical TB history. Patients who had prior PTB on CXR but had not received a clinical diagnosis and anti-TB therapy were included for analysis. Live birth, clinical pregnancy, and miscarriage rates were compared between the untreated PTB and non-PTB groups.The untreated PTB group had significantly lower clinical pregnancy (31.7%Untreated PTB was associated with adverse pregnancy outcomes after IVF-ET, especially in patients with unexplained infertility, highlighting the clinical significance of PTB in this specific patient population.

Lung cancer is the most frequent cancer worldwide with a poor prognosis. Identification of novel cancer targets and useful therapeutic strategies without toxicity are urgently needed. In this study, we screened natural products for anticancer bioactivity in a library consisting of 429 small molecules. We demonstrated for the first time that daurisoline, a constituent of Rhizoma Menispermi, repressed lung cancer cell proliferation by inducing cell cycle arrest at the G1 phase. Furthermore, daurisoline was found not only to suppress the growth of lung tumor xenografts in animals without obvious side effects, but also to inhibit cell migration and invasion. Mechanistically, quantitative proteomics and bioinformatics analyses, Western blotting and qRT-PCR confirmed that daurisoline exerted its anticancer effects by inhibiting the expression levels of β-catenin and its downstream targets c-myc and cyclin D1. Furthermore, our data from Drug Affinity Responsive Target Stability (DARTS), isothermal titration calorimetry (ITC) and a series of functional assays demonstrated that daurisoline could target HSP90 directly and disrupt its interaction with β-catenin, therefore increasing the ubiquitin-mediated proteasomal degradation of β-catenin. This study reveals that daurisoline could be a promising therapeutic strategy for the treatment of lung cancer.

Metastasis is the main factor of treatment failure in cancer patients, but the underlying mechanism remains to be elucidated and effective new treatment strategies are urgently needed. This study aims to explore novel key metastasis-related microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). By comparing miRNA profiles of the highly metastatic ESCC cell sublines, we established through serial in vivo selection with the parental cells, we found that the expression level of miR-515-3p was lower in ESCC tumor tissues than adjacent normal tissues, further decreased in metastatic tumors, and moreover, markedly associated with advanced stage, metastasis and patient survival. The in vitro and in vivo assays suggested that miR-515-3p could increase the expression of the epithelial markers as well as decrease the expression of the mesenchymal markers, and more importantly, suppress invasion and metastasis of ESCC cells. Mechanistically, we revealed that miR-515-3p directly regulated vimentin and matrix metalloproteinase-3 (MMP3) expression by binding to the coding sequence and 3′untranslated region, respectively. In addition, the data from whole-genome methylation sequencing and methylation-specific PCR indicated that the CpG island within miR-515-3p promoter was markedly hypermethylated in ESCC cell lines and ESCC tumor tissues, which may lead to deregulation of miR-515-3p expression in ESCC. Furthermore, our preclinical experiment provides solid evidence that systemic delivery of miR-515-3p oligonucleotide obviously suppressed the metastasis of ESCC cells in nude mice. Taken together, this study demonstrates that miR-515-3p suppresses tumor metastasis and thus represents a promising prognostic biomarker and therapeutic strategy in ESCC.

Background: Colorectal cancer (CRC) is a high incidence of malignant tumors that lacks highly effective and targeted drugs and thus it is in urgent need of finding new specific molecular targets. Methods and Results: In this study, by using WST-1 (Highly water-soluble tetrazolium salt-1) and colony formation assays, we found that C20orf27 (chromosome 20 open reading frame 27), a functionally unknown protein, enhanced the growth and proliferation of CRC cells. The nude mouse tumor formation experiments verified that C20orf27 promoted the growth of CRC. Signal pathway analysis identified the TGF&beta, R-TAK1-NFĸB cascade as a mediator in C20orf27-induced CRC progression. Inhibition experiments using NFĸB inhibitors reversed this progression. Co-immunoprecipitation showed that C20orf27 promoted the activation of the TGF&beta, R-TAK1-NFĸB pathway by interacting with PP1c (the catalytic subunit of type 1 phosphatase). Conclusions: Our results firstly characterized the functional role and molecular mechanism of C20orf27 in driving CRC growth and proliferation through the TGF&beta, R-TAK1-NFĸB pathway, suggesting its potential as a novel CRC candidate therapeutic target and tumor marker.

The aim was to investigate how the PI3K/Akt pathway is involved in the protection of dexmedetomidine against propofol. The hippocampal neurons from fetal rats were separated and cultured in a neurobasal medium. Cell viability was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then neurons were pretreated with different concentrations of dexmedetomidine before 100 μmol/L propofol was added. Akt, phospho-Akt (p-Akt), Bad, phospho-Bad (p-Bad), and Bcl-xL were detected by Western blot. Also, neurons were pretreated with dexmedetomidine alone or given the inhibitor LY294002 before dexmedetomidine pretreatment, and then propofol was added for 3 h. The results demonstrated that propofol decreased the cell viability and the expression of p-Akt and p-Bad proteins, increased the level of Bad, and reduced the ratio of Bcl-xL/Bad. Dexmedetomidine pretreatment could reverse these effects. The enhancement of p-Akt and p-Bad induced by dexmedetomidine was prevented by LY294002. These results showed that dexmedetomidine potently protected the developing neuron and this protection may be partly mediated by the PI3K/Akt pathway.

People with cognitive deficits or executive dysfunction are often overweight or obese. Several human neuroimaging studies have found that executive function (EF) predicts food intake and weight gain; however, fewer studies have investigated the relationship between EF and weight loss. The Stroop task is a classic measure of EF that is used in many neuroimaging studies. In the present work, functional near infrared spectroscopy (fNIRS) data were collected during performance of the Stroop task from a sample of overweight or obese adolescents and young adults (n = 31) who participated in a summer fitness and weight loss camp. We assessed the Stroop effect by interference in the reaction time (RT) to visual challenges, and by alterations in levels of oxygenated hemoglobin, as detected by fNIRS. In line with previous studies, we found that the Stroop effect was successfully induced by different visual task conditions among obese/overweight individuals. Moreover, our results reveal that better Stroop task performance is correlated with greater weight loss over a4-weekfitness intervention. Indeed, behavioral data demonstrated that reduced RT interference predicted a greater percentage of weight loss. Moreover, overweight/obese individuals with a greater hemodynamic response in the left ventrolateral and bilateral dorsolateral prefrontal cortex due to the Stroop effect lost more weight during the short-term fitness intervention than participants with lower levels of activation of these neural regions. Overall, our results support a role for prefrontal cortex-mediated EF in influencing food intake and weight loss outcomes in a population of a previously unstudied age.

Background: The prognosis of esophageal squamous cell carcinoma (ESCC) is generally poor, and the identification of molecular markers related to the regulation of ESCC invasion and migration is important. Methods and Results: In this study, we report that ring finger protein-128 (RNF128) enhances the invasiveness and motility of ESCC cells by using transwell assays and Western blotting. A xenograft nude mouse model showed that RNF128 promotes the metastasis of ESCC cells in the lung. A signal pathway analysis identified the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK)/matrix matalloproteinases 2 (MMP-2) cascade as a mediator of RNF128-induced enhancement of ESCC progression. Inhibition experiments using inhibitors of EGFR, ERK kinase (MEK)/extracellular-signal-regulated-kinase (ERK), and MMP-2 reversed this progression. Co-immunoprecipitation demonstrated that RNF128 promotes the activation of the EGFR/ERK/MMP-2 pathway by interacting with p53 and p53 interacting with EGFR. Conclusion: Our results establish the functional role of RNF128 in driving the invasion and metastasis of ESCC through the EGFR/MAPK/MMP-2 pathway, implicating its potential as a candidate therapeutic target and prognostic biomarker for ESCC.

Resistance to tumor‐necrosis‐factor‐related apoptosis‐inducing ligand (TRAIL) of cancer cell remains a key obstacle for clinical cancer therapies. To overcome TRAIL resistance, this study identifies curcumol as a novel safe sensitizer from a food‐source compound library, which exhibits synergistic lethal effects in combination with TRAIL on non‐small cell lung cancer (NSCLC). SILAC‐based cellular thermal shift profiling identifies NRH:quinone oxidoreductase 2 (NQO2) as the key target of curcumol. Mechanistically, curcumol directly targets NQO2 to cause reactive oxygen species (ROS) generation, which triggers endoplasmic reticulum (ER) stress‐C/EBP homologous protein (CHOP) death receptor (DR5) signaling, sensitizing NSCLC cell to TRAIL‐induced apoptosis. Molecular docking analysis and surface plasmon resonance assay demonstrate that Phe178 in NQO2 is a critical site for curcumol binding. Mutation of Phe178 completely abolishes the function of NQO2 and augments the TRAIL sensitization. This study characterizes the functional role of NQO2 in TRAIL resistance and the sensitizing function of curcumol by directly targeting NQO2, highlighting the potential of using curcumol as an NQO2 inhibitor for clinical treatment of TRAIL‐resistant cancers., This study discovered that curcumol sensitizes lung cancer cell to tumor‐necrosis‐factor‐related apoptosis‐inducing ligand (TRAIL)‐mediated apoptosis. Curcumol exhibits synergistic lethal effects with TRAIL on cancer cell by directly targeting quinone oxidoreductase 2 (NQO2) to induce reactive oxygen species, triggering ER stress‐C/EBP homologous protein (CHOP)‐death receptor 5 (DR5) signaling to combat TRAIL‐resistant cancer.

Volatile organic compounds (VOCs) are an important source of industrial stench. This study was aimed at sampling and analyzing the stench source and its impact on the sensitive spot residential areas, concentrating on certain automobile manufacturing enterprise. The odor concentration and VOCs species of each vent stack, plant boundary, and sensitive spot in the enterprise were determined for November 15 and 17, 2016 via qualitative and quantitative analysis using the triangle odor bag method and gas pre-concentration system-gas chromatography-mass spectra. The results show that the odor concentrations of all vent stacks in the original equipment manufacturing plant and the engine plant were below the criterion level, those of the plant boundaries in the engine plant were below the limits, and those of the plant boundaries and sensitive spots in the original equipment manufacturing plant exceeded the allowed standards. A total of 54 VOCs species were identified, including aromatics, halogenated compounds, alkanes, alkene, cycloalkanes, ketones, esters, ethers, alcohols, sulfur compounds, and oxygen ring compounds. Halogenated compounds were the most abundant VOCs species, followed by aromatics. As a result, aromatics and halogenated compounds are the representative odorants in automobile making. 1,3-Butadiene and ethyl toluene were selected to be the typical odorants of sensitive spots according to mass concentration, detector odor threshold, and threshold dilution multiples of characteristic VOCs species in sensitive spots. The results show that the majority of characteristic VOCs species were from paint composition through the qualitative analysis based on paint used in coating shops. 1,3-Butadiene, which contributed the most to odor pollution, excluding the impact of other emission sources on sensitive spots, originates from spraying and drying processes of coating shops in the original equipment manufacturer. It is recommended that the enterprise should adopt environmentally friendly paints with low VOCs components or RTO purification equipment with higher processing efficiency to reduce the impact of stench on the sensitive residential areas from automobile making.

Recent studies have suggested a link between executive function (EF) and obesity. Studies often adopt body mass index (BMI), which reflects the distribution of subcutaneous fat, as the sole marker of obesity; however, BMI is inappropriate to distinguish central obesity, which indicates the centralized distribution of visceral fat. Visceral fat compared with subcutaneous fat represents greater relative lipid turnover and may increase the risk of cognitive decline in older adults. However, the relationship between EF and central obesity is largely unknown, particularly in young adults. Therefore, we used waist circumference (WC) as a marker of central obesity and investigated different sensitivities between BMI and WC in the brain function. A total of 26 healthy young adults (aged 18–25 years; 42% female) underwent functional near-infrared spectroscopy assessments. EF was assessed using the Stroop task, which is a classical measurement of EF. A significant Stroop effect was observed in the behavioral and hemodynamic data. In addition, we observed that behavioral interference on the Stroop task varied much more in subjects with higher BMI and WC than those subjects with lower. Elevated BMI and WC were associated with a decreased hemodynamic response during the Stroop task specifically in the prefrontal cortex (PFC). Compared to BMI, WC was more closely connected with inhibitory control and revealed right lateralized PFC activation. Our findings suggest that WC is a reliable indicator of brain function in young adults and propose a relationship between EF and central obesity.

6-O-Angeloylenolin (6-OA), a sesquiterpene lactone isolated from Centipeda minima (L.) A. Br. (Compositae), has been used to treat respiratory diseases for centuries. However, whether and how 6-OA exerts anticancer effects against lung cancer remains to be elucidated. In this study, we showed that 6-OA markedly suppressed the cell viability and colony formation of lung cancer cells H1299 and A549, with no significant toxic effect on non-cancer cells HBE. Annexin V/7-AAD assay revealed that 6-OA induced cell apoptosis in dose- and time-dependent manners, which was further confirmed by the increased expression of cleaved caspase-3. To uncover the molecular mechanism how 6-OA exerts its anticancer effects, SILAC quantitative proteomics was performed to identify 6-OA-regulated proteins in lung cancer cells. Ingenuity Pathway Analysis revealed that these 6-OA-regulated proteins were mainly involved in Nrf2-mediated oxidative stress response, which was confirmed by the nuclear translocation of Nrf2 upon 6-OA treatment. Moreover, we found that 6-OA stimulated the accumulation of reactive oxygen species (ROS), whereas inhibition of ROS generation with N-acetyl l-cysteine could block the 6-OA-induced anticancer effects. Furthermore, blockade of cellular anti-oxidative system by Nrf2 knockdown significantly augmented the 6-OA-induced apoptosis. Taken together, we demonstrated that 6-OA exerts its anticancer effects by generating ROS, and inhibition of Nrf2 anti-oxidative system potentiated these effects. These results suggest that 6-OA may be used to treat lung cancer, with better outcome by combining with Nrf2 inhibitor to block Nrf2 pathway.

In connection with the problems that the automobile passive stabilizer bar can’t reflect the road conditions in real time and it is difficult to simultaneously meet the requirements of ride comfort and manipulation stability, this paper describes a kind of control system and test platform of the automobile automatic stabilizer bar. The control system uses speed sensor, steering angle sensor, roll angle sensor, lateral acceleration sensor and displacement sensor to simulate a variety of vehicle’s real driving conditions in the laboratory environment. According to the formulated control strategy, the microcontroller will send different instructions to make the executive mechanism act reasonably and in time. Then the test platform is established in the laboratory environment by the method of semi-physical simulation. The system can be designed according to the different needs of the vehicle and ensures the vehicle’s safety and comfort to the maximum.

Background Astigmatism is one of the most significant obstacles for achieving satisfactory visual function. This study was to evaluate the influence of astigmatism on contrast sensitivity (CS) and higher-order aberrations. Methods CS, accommodation response and wavefront aberration were measured in 113 patients with astigmatism, aged 18 - 36 years. Both single and binocular visual performance were examined under four lighting conditions: photopia, photopia with glare, scotopia and scotopia with glare respectively. Accommodation response was classified as normal, abnormal and low. The contribution of the power and axis of astigmatism to CS, accommodation response and wavefront aberration was analyzed. Results As the dioptric power of astigmatism increased, the loss of CS spatial frequency changed from high to intermediate, and then to low frequency. CS scores varied at different illuminance levels, descending in the following sequence: photopia, photopia with glare, scotopia, and scotopia with glare. However, the normal accommodation group showed better CS values under photopia with glare than without glare. The range of influenced direction of sine-wave gratings remained mostly at the meridian line of high dioptric power, which would be expanded when optical accommadation attenuated. The patients with symmetrical astigmatism got higher CS scores with binoculus vision than with dominant eye vision, while the patients with asymmetrical astigmatism did this only at scotopia with glare. Among higher-order aberrations, coma aberration, secondary coma aberration and the total higher order aberration were influenced by astigmatism, all of which rising with the power of astigmatism increased. Conclusions Reducing astigmatism might improve the performance of visual function. Not only the power of astigmatism should be cut down, but also the binocular axes should be made symmetrically.

The aim of the present study was to investigate the effects of cytomegalovirus (CMV) infection on the prognosis of inflammatory bowel disease (IBD). Various databases were searched using a combination of keywords associated with CMV infection and IBD. Subsequent to the selection of relevant studies in line with strict inclusion and exclusion criteria, a meta-analysis was conducted using the Stata 12.0 software. A total of 195 studies were initially retrieved, including 28 studies in Chinese and 167 in English. Following the exclusion of unsuitable studies, 7 cohort studies with 374 IBD patients were included in the meta-analysis. The results of the present study identified significant differences between patients with and without CMV infection regarding the disease duration of IBD [standardized mean difference, -0.81; 95% confidence interval (CI), -1.19 to -0.43; P

Aims Nateglinide is a meglitinide analogue with antidiabetic action. A recent study showed that SLCO1B1 (which codes the OATP1B1 gene, also known as OATP-C, OATP2) is a major determinant which markedly affects the pharmacokinetics of repaglinide. Our objective was to assess the association between single nucleotide polymorphisms (SNPs) of SLCO1B1 and the pharmacokinetics of nateglinide. Methods Seventeen healthy volunteers with different SLCO1B1 genotypes (11 with 521TT, four with 521TC and two with 521CC) were enrolled in this study. Each was given a single oral dose of 90 mg nateglinide. Plasma concentrations of nateglinide were measured up to 8 h by HPLC. Results The Cmax and AUC(0,∞) of nateglinide were 83% (P = 0.002) and 82% (P = 0.001) higher in the SLCO1B1521TC subjects (n = 4), and 76% (P = 0.016) and 108% (P = 0.001) higher in the SLCO1B1521CC subjects (n = 2) than in the SLCO1B1521TT subjects (n = 11), respectively. The t1/2 of nateglinide in SLCO1B1521CC subjects was 78% longer than that in 521TT subjects (P = 0.036). The difference in tmax values among the three genotypic groups was not statistically significant. Conclusions Our results suggest that OATP1B1-mediated hepatic uptake of nateglinide may be the prior step for its metabolism and elimination. SLCO1B1521T > C SNP might play an important role in the pharmacokinetics of nateglinide.

Objective We investigated the linkage between SNPs in exon 12 (C1236T), exon 21 (G2677T/A) and exon 26 (C3435T) of MDR1, and explored the effect of linked polymorphism on the absorption of talinolol after a single oral dose of 100 mg. Methods The genotype of 192 healthy Chinese volunteers was determined using PCR-RFLP with respect to the MDR1 alleles of interest, C1236T, G2677T/A and C3435T. Linkage disequilibrium was analyzed using PHASE software. Consecutive eligible subjects received a single oral dose of 100 mg talinolol. Venous blood samples were taken at intervals up to 60 h post dose for HPLC analysis of plasma concentration of talinolol to obtain a pharmacokinetic profile. Results Linkage disequilibrium existed between exon 21 (G2677T/A) and exon 26 (C3435T), exon 12 (C1236T) and exon 21 (G2677T/A), but not between exon 12 (C1236T) and exon 21 (G2677T/A). AUC (0,3h), AUC (0,∞), C max and C max /AUC (0,∞), used as indices of talinolol absorption, were not significantly different between the genotype groups of 2677GG/3435TT, 2677TT/3435TT, 2677GT/3435CT and 2677AT/3435CT. For these 4 groups, AUC(0,3h) were 436.8 ± 50.1, 510.1 ± 86.3, 466.1 ± 77.8 and 437.2 ± 73.4 (μg × h/l) and the C max /AUC (0,∞) were 0.097 ± 0.018, 0.093 ± 0.022, 0.105 ± 0.014 and 0.102 ± 0.027 (h −1 ), respectively. ( P > 0.05). Conclusions The linked MDR1 polymorphisms in exon 21 G2677T/A and exon 26 C3435T apparently did not contribute to the absorptive pharmacokinetics of a single oral dose of 100 mg talinolol.

Background: Human cytochrome P450 2A13 (CYP2A13) is involved in the activation of numerous toxicants and carcinogens, especially in the metabolic activation of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a major tobacco-specific carcinogen. A functionally significant coding single nucleotide polymorphism (C3375T) in exon 5 of CYP2A13, which results in an amino acid substitution of Arg 257 to Cys, has been recently reported to exist in White, Black, Hispanic, and Asian individuals, with the variant 3375T allele frequencies being 1.9%, 14.4%, 5.8% and 7.7%, respectively. Since genetic background differs between ethnic groups, our present study aims to characterize the CYP2A13 Arg257Cys polymorphism in Chinese. Methods: 258 healthy Chinese Han volunteers were involved in this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was employed to genotype for the Arg257Cys polymorphism. Results: Of all the 258 subjects, 27 (10.5%) heterozygotes and 1 (0.4%) homozygote for the 257Cys allele were detected. The frequency of the variant 257Cys allele in this Chinese population was 5.6% (95%CI: 4.2–7.0%). Conclusion: The CYP2A13 Arg257Cys variant represents a common polymorphism in Chinese, with the 257Cys allele frequency being similar to the Hispanic and Asian groups, but significantly lower than the Black. D 2004 Published by Elsevier B.V.

Background: The motive of this study was to investigate the collaboration between MDR1 gene polymorphisms and anesthetic effects following pediatric tonsillectomy. Methods: All together 178 children undergoing tonsillectomy with preoperative sevoflurane–remifentanil anesthesia were selected. In order to determine MDR1 gene polymorphisms of 3435C > T, 1236C > T, and 2677G > T/A, polymerase chain reaction–restriction fragment length polymorphism was used. Mean arterial pressure (MAP), diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) at T0 (5 mins after the repose), T1 (0 min after tracheal intubation), T2 (5 mins after the tracheal intubation), T3 (0 min after the tonsillectomy), T4 (0 min after removal of the mouth-gag) and T5 (5 min after the extubation) were observed. The visual analog scale (VAS), the face, legs, activity, cry, and consolability (FLACC) pain assessment, and Ramsay sedation score were recorded after the patients gained consciousness. The adverse reactions were also observed. Results: As compared to the CT + TT genotype of MDR1 1236C > T, the time of induction, respiration recovery, eye-opening, and extubation of children with the CC genotype was found to be shorter (all P T CC genotype was found to be superior to those carrying the CT + TT genotype.

Aim: To detect 388G>A and 521T>C variant alleles in the organic anion transporting polypeptide-1B1 (OATP1B1, encoding gene SLCO1B1) gene. Methods: One hundred and eleven healthy volunteers were screened for OATP1B1 alleles in our study. PCR-restriction fragment length polymorphism was used to identify the 388G>A polymorphism and a 1-step tetra-primer method was developed for the determination of 521T>C mutation. Results: The frequencies of the 388G>A and 521T>C variant alleles in the Chinese population were 73.4% and 14.0%, respectively. The frequencies of the SLCO1B1*1 b and *15 haplotypes were 59.9% and 14.0%, respectively. Conclusion: The SLCO1B1*1 b and SLCO1B1*15 variants are relatively common in the Chinese population. Their frequencies are similar to that in the Japanese, but significantly different from that in Caucasians and blacks.

To investigate the pharmacokinetics of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF) in Chinese adult liver transplant patients.Thirty-eight liver transplant patients (male 30, female 8) receiving MMF 1.0 g, twice daily in accordance with the recommended regimen were included in this study. Plasma MPA concentrations were measured by high performance liquid chromatography at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software.The plasma MPA concentration-time curve was characterized with an early sharp peak reached at 0.5 - 6.0 h after oral administration. And in some patients there was a small second peak due to enterohepatic circulation of mycophenolic acid glucuronide (MPAG), which underwent deglucuronidation and re-absorption as MPA at 4 to 12 h postdose. The mean peak plasma concentration (C(max)) and area under concentration-time curve (AUC(0-12 h)) were (12 +/- 7) microg x mL(-1) and (44 +/- 16) microg x h x mL(-1), respectively. However, a large variability of pharmacokinetic parameters existed in these patients.In view of the inter-individual variability of MMF pharmacokinetics, plasma MPA concentration should be monitored routinely after MMF administration for individual patient.

To investigate the association of CYP2C9*3 and *6 with hyperlipidaemia in Chinese.Four hundred and seventy-six Chinese participated in the study, including 211 uncomplicated hyperlipidaemic patients and 265 healthy controls. PCR-RFLP was used to identify CYP2C9*3 and *6.CYP2C9*6 was not detected in this study. The allelic frequency of CYP2C9*3 was 0.039 (95% CI 0.022, 0.056). A nonsignificant difference existed in CYP2C9*3 frequencies between males and females (P = 0.605, OR = 1.194, 95% CI 0.610, 2.336), patients and controls (P = 0.063, OR = 0.506, 95% CI 0.244, 1.049) in the total population. However, in the female group, CYP2C9*3 frequency in patients with hyperlipidaemia was significantly lower than that in controls (P0.0001, OR = 0.062, 95% CI 0.008, 0.476).The association of CYP2C9*3 with hyperlipidaemia was specific for females in this Chinese population.