Temporal Change in Paravalvular Leakage after Transcatheter Aortic Valve Replacement with a Self-Expanding Valve: Impact of Aortic Valve Calcification.

BACKGROUND: In patients undergoing transcatheter aortic valve replacement (TAVR), the severity of paravalvular leakage (PVL) may change during follow-up, however its mechanism is poorly understood. We aimed to explore temporal changes in PVL and possible predictors following TAVR. METHODS: A retrospective analysis was performed of all patients who had received a self-expanding valve. Multi-detector computed tomography was performed as pre-TAVR evaluation, including assessment of aortic valve calcification (AVC). The patients received transthoracic echocardiography at baseline and 30 days, 6 months, and 1 year after TAVR. RESULTS: In total, 93 patients who had received a self-expanding valve during TAVR were identified. Various degrees of PVL were seen in 63 patients, with moderate/severe PVL in 21 (22.6%). In multivariate analysis, the predictors of moderate/severe PVL were: chronic pulmonary disease, high degree of AVC, and an increased annulus perimeter. After 1 year of follow-up, PVL deteriorated from mild to moderate in 2 patients, while an improvement of ≥ 1 grade was seen in 25 patients. Of 21 patients with post-TAVR moderate/severe PVL, 9 had an improvement of ≥ 1 grade and 12 did not. The degree of AVC was significantly lower in those with PVL improvement (Agatston score 3068 ± 1816 vs. 6418 ± 3222; p = 0.01). AVC was a good predictor for an improvement in PVL, and the area under the receiver operating characteristic curve was 0.82 (95% confidence interval = 0.63-1.00, p = 0.01), with a cut-off value of 5210. CONCLUSIONS: In this study, 43% (9/21) of the patients with moderate/severe PVL after self-expanding TAVR had an improvement of ≥ 1 grade within 1 year, and a low degree of AVC was predictive of this improvement.

Efficacy of pelvic floor training with surface electromyography feedback for female stress urinary incontinence.

AIMS: The aim of the study is to compare the efficacy of an 8-week pelvic floor muscle training program with surface electromyography feedback, performed in different body positions (supine, sitting, and standing), in women with stress urinary incontinence. DESIGN: This is a prospective observational study performed January 2014 to May 2016. METHODS: The training program was performed by 110 women with stress urinary incontinence, each completing 4 individual training sessions. The main outcome was the electromyography activity of the pelvic floor muscles and of the synergistic abdominal muscles. Outcome measures were evaluated at 4 time points, namely at baseline and at 2, 4, and 8 weeks of training. RESULTS: A notable effect of training was identified at week 2, which was sustained through to week 8. Training yielded a significant improvement in increased sustained voluntary contraction of the pelvic floor muscles in all 3 positions. The efficacy of training was influenced by the duration of training, age, body mass index, and history of vaginal delivery. CONCLUSION: Training of the pelvic floor muscles, with positive reinforcement by surface electromyography feedback of the pelvic floor muscles and of the synergistic abdominal muscles, was effective for the treatment of stress urinary incontinence in women and should be considered as a feasible option by healthcare providers.

Predicting stroke volume and arterial pressure fluid responsiveness in liver cirrhosis patients using dynamic preload variables: A prospective study of diagnostic accuracy.

BACKGROUND: Predicting whether a fluid challenge will elicit 'fluid responsiveness' in stroke volume (SV) and arterial pressure is crucial for managing hypovolaemia and hypotension. Pulse pressure variation (PPV), SV variation (SVV) and the plethysmographic variability index (PVI) have been shown to predict SV fluid responsiveness, and the PPV/SVV ratio has been shown to predict arterial pressure fluid responsiveness under various conditions. However, these variables have not been investigated in liver cirrhosis patients. OBJECTIVE: The objective was to evaluate SV and arterial pressure fluid responsiveness in liver cirrhosis patients by using dynamic preload and vascular tone variables. DESIGN: A prospective study of diagnostic accuracy. SETTINGS: A single-centre trial conducted from November 2013 to April 2015. PATIENTS: Thirty-one adult patients, recipients of a living donor liver transplantat. INTERVENTION: An intraoperative fluid challenge with 10 ml kg of 0.9% normal saline. MAIN OUTCOME MEASURES: PPV, SVV, cardiac index and systemic vascular resistance index were measured using the Pulse index Continuous cardiac system. The PVI and perfusion index were measured using the Masimo Radical 7 co-oximeter. The PPV, SVV and PVI were measured to investigate SV fluid responsiveness, and the PPV/SVV ratio, perfusion index and systemic vascular resistance index were measured to investigate arterial pressure fluid responsiveness. RESULTS: The areas under the receiver operating characteristic curves for PPV, SVV and PVI were 0.794, 0.754 and 0.800, respectively (all P < 0.001). The cut-off values for PPV, SVV and PVI were 10% (sensitivity 78.3%, specificity 79.5%), 12% (sensitivity 69.6%, specificity 71.8%) and 11% (sensitivity 95.7%, specificity 59.0%), respectively. However, all investigated vascular tone variables failed to predict arterial pressure and fluid responsiveness. CONCLUSION: Dynamic preload variables predicted SV fluid responsiveness. Therefore, these variables can be used for fluid management in liver cirrhosis patients receiving mechanical ventilation. In contrast, vascular tone variables did not predict arterial pressure fluid responsiveness in liver cirrhosis patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01971333.

Preparative resolution of gatifloxacin enantiomers with pre-column esterification strategy and comparing their enantioselectivity to bacteria and antibody.

Gatifloxacin (GFX) is a kind of chiral fluoroquinolones compound due to the methyl group at the C-3 position of the piperazine ring[1]. Although the enantiomers of GFX show similar levels of antimicrobial activity and pharmacokinetics[2], the other biological activities (i.e., toxicity or enantioselective recognition to various receptors in vivo) of GFX enantiomers have not yet been studied. With this in mind, we developed a rapid and cost-effective high performance liquid chromatographic (HPLC) separation procedure for GFX enantiomers with a pre-column esterification strategy. With significant enhancement of drug solubility and optimization for chromatographic conditions, the proposed method was scaled up to preparative HPLC to obtain optical active S-(-)- and R-(+)-GFX. The antibacterial activities of GFX enantiomers after preparative separation were further verified by measuring the Minimum Inhibitory Concentration (MIC) values against Escherichia coli ATCC 25922. In addition, the binding selectivity of GFX enantiomers to protein receptor were evaluated by antibody using enzyme-linked immunosorbent assay (ELISA) for the first time.

Impact of conduction disturbances on left ventricular mass regression and geometry change following transcatheter aortic valve replacement.

Our study aimed to compare the difference of LV mass regression and remodeling in regard of conduction disturbances (CD) following transcatheter aortic valve replacement (TAVR). A prospective analysis of 152 consecutive TAVR patients was performed. 53 patients (34.9%) had CD following TAVR, including 30 (19.7%) permanent pacemaker implantation and 23 (15.2%) new left bundle branch block. In 123 patients with 1-year follow-up, significant improvement of LV ejection fraction (LVEF) (baseline vs 12-month: 65.1 ± 13.2 vs 68.7 ± 9.1, P = 0.017) and reduced LV end-systolic volume (LVESV) (39.8 ± 25.8 vs 34.3 ± 17.1, P = 0.011) was found in non-CD group (N = 85), but not in CD group (N = 38). Both groups had significant decrease in LV mass index (baseline vs 12-month: 148.6 ± 36.9 vs. 136.4 ± 34.7 in CD group, p = 0.023; 153.0 ± 50.5 vs. 125.6 ± 35.1 in non-CD group, p < 0.0001). In 46 patients with 3-year follow-up, only non-CD patients (N = 28) had statistically significant decrease in LV mass index (Baseline vs 36-month: 180.8 ± 58.8 vs 129.8 ± 39.1, p = 0.0001). Our study showed the improvement of LV systolic function, reduced LVESV and LV mass regression at 1 year could be observed in patients without CD after TAVR. Sustained LV mass regression within 3-year was found only in patients without CD.

Efficacy of bio-assisted pelvic floor muscle training in women with pelvic floor dysfunction.

OBJECTIVES: To evaluate the efficacy of 12-week pelvic floor muscle training (PFMT) using bio-assisted surface electromyography (EMG) feedback in women with complex pelvic floor dysfunction (PFD); to further differentiate the effect of exercise adherence from the biofeedback per se; and to assess and compare the severities of overactive bladder (OAB) symptoms, stress urinary incontinence (SUI), and stage of prolapse with the women's perception of symptom cure or improvement following the program. STUDY DESIGN: This prospective observational study was conducted between December 2015 and November 2018 at a medical center in Taiwan. It included 83 women with PFD, manifesting solely as either OAB or SUI with (group 1) or without (group 2) concomitant stages I and II pelvic organ prolapse (POP). All women underwent a 12-week bio-assisted PFMT. The main outcome was the electromyographic activity of the pelvic floor muscles (PFMs). The severities of OAB symptoms, SUI, and stage of POP were assessed both subjectively and objectively before and after the intervention. RESULTS: A notable improvement of PFM function was identified after 12 weeks of training in all women with PFD. The number of effective PFM contractions achieved during bio-assisted PFMT was positively correlated with the improvement of PFM function in both groups of women in different body positions, except in the standing position in group 2. Exercise adherence, however, had no significant impact on the efficacy of the training. There was a significant improvement over time and high consistency between subjective and objective improvements of OAB symptoms and SUI severity after the completion of PFMT. Nonetheless, only the Ba point of the POP-Quantification system in women with POP showed a significant improvement after the intervention. CONCLUSION: PFMT using surface EMG biofeedback significantly improves PFM function in women with complex PFD, and thus, has a significant therapeutic effect on OAB, SUI, and bladder prolapse.

Antidepressant mechanisms of venlafaxine involving increasing histone acetylation and modulating tyrosine hydroxylase and tryptophan hydroxylase expression in hippocampus of depressive rats.

Venlafaxine (VEN) is a widely used antidepressant as a serotonin-reuptake and norepinephrine-reuptake inhibitor. It is used primarily in depression, especially with generalized anxiety disorder or chronic pain. This medicine is of interest because its mechanisms involved multiple aspects. In the current study, the antidepressant action of VEN was investigated by studying the histone acetylation and expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) in rats exposed to chronic unpredicted stress (CUS) for 28 days. Male Sprague-Dawley rats were divided into a control group, VEN-treated control group, CUS group, and VEN-treated CUS group. VEN (23.4 mg/kg once daily) was administered to rats by intragastric gavage, whereas the same volume of vehicle was given to rats in the control and model groups. Rat behaviors, acetylated H3 at lysine 9 (acH3K9), acetylated H3 at lysine 14 (acH3K14), acetylated H4 at lysine 12 (acH4K12), histone deacetylase 5, and TH and TPH expression in the hippocampus were determined. Chronic VEN treatment significantly relieved the anxiety- and depression-like behaviors, prevented the increase of histone deacetylase 5 expression and decrease of acH3K9 level, and promoted TH and TPH protein expression in the hippocampus of CUS rats. The results suggest that the preventive antidepressant mechanism of VEN is partly involved in the blocking effects on histone de-acetylated modification and then increasing TH, TPH expression.

Intentional combination of ProGlide and Angio-Seal for femoral access haemostasis in transcatheter aortic valve replacement.

BACKGROUND: To describe and evaluate the intentional combination of Angio-Seal (AS) and Perclose ProGlide (PP) in achieving haemostasis in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR). METHODS: This study cohort was divided into two groups: dual PP versus one AS with one PP (AS + PP) used for common femoral artery haemostasis. The baseline, procedural characteristics and all outcomes (defined according toVARC-2 criteria) were prospectively collected and retrospectively compared. RESULTS: Overall, a total of 151 consecutive patients (68 men; 80.9 ±â€¯7.3 years old) were evaluated. Of these, 51 patients (33.8%) underwent TAVR using the dual PP, and 100 (66.2%) using one AS with one PP. There were no significant differences in the baseline characteristics of both patient groups, except higher incidence of chronic pulmonary disease in dual PP group (21.6% vs 7%, P = 0.009). Patients in AS + PP group had lower rate of arterial stricture (21.6% vs 8%, P = 0.017), arterial dissection (13.7% vs 4.0%), requiring endovascular intervention for puncture site issues (21.6% vs 9.0%, P = 0.031). Less procedural time (139.8 ±â€¯36.9vs97.9 ±â€¯31.4 min, P < 0.001) & contrast medium consumption (223.9 ±â€¯88.3vs174.1 ±â€¯49.7 ml, P < 0.001) were also observed in AS+PP group. There were no statistically significant differences between 2 groups in regards of closure device failure, major and minor vascular complications, nor major and minor bleeding. CONCLUSIONS: Intentional combination of one PP and one AS for femoral access haemostasis in patients undergoing TAVR is feasible and safe, with low risk of vascular and bleeding complications.

Frequency and Significance of Intravascular Hemolysis Before and After Transcatheter Aortic Valve Implantation in Patients With Severe Aortic Stenosis.

Intravascular hemolysis (IVH) has been identified in patients with surgical prosthetic valves, but few have been reported after transcatheter aortic valve implantation (TAVI). We conducted a prospective analysis of 64 TAVI patients. The hemolysis profiles were collected at baseline and 6 months after TAVI. The echocardiography was performed at baseline and 6 months after TAVI. There are 14 patients (21.9%) with IVH before and 24(37.5%) after TAVI. The serum haptoglobin values before and 6 months after TAVI are 126.7 ± 75.1 vs 86.3 ± 57.1 mg/dl (p < 0.001). More ≥moderate paravalvular leakage (PVL) (50% vs 7.5%, p < 0.001), bicuspid aortic valve (BAV) (33.3% vs 5.0%, p = 0.004), use of 23 mm prosthesis (29.2% vs 7.5%, p = 0.03), higher residual valvular pressure gradient (17.9 ± 6.8 mm Hg vs 14.7 ± 5.7 mm Hg, p = 0.05), and lower effective orifice area index (1.05 ± 0.21 vs 1.21 ± 0.29, p = 0.03) were observed in patients with post-TAVI IVH. On multivariate regression analysis, BAV and ≥moderate PVL are independently related to post-TAVI IVH. With log-rank test, 1-year rates of readmission due to cardiovascular cause were significantly higher in patients with post-TAVI IVH (odds ratio 4.5; 95% confidence interval 1.3 to 15.6; p = 0.02), after adjusting age and gender. In conclusion, ≥moderate PVL and BAV are predictors of post-TAVI IVH, which is associated with increased cardiovascular readmission in 1-year follow-up.

Simultaneous electrochemical determination of uric acid and ascorbic acid on a glassy carbon electrode modified with cobalt(II) tetrakisphenylporphyrin.

A cobalt(II) tetrakisphenylporphyrin (Co(II)TPP) film modified glassy carbon electrode (Co(II)TPP-GCE) was prepared by just coating Co(II)TPP solution on the surface of the electrode. It can be used for the simultaneous determination of ascorbic acid and uric acid. The anodic peaks of AA and UA can be separated well. Owing to the strongly hydrophobic property of porphyrin, the modified electrode has good stability and long life. The linear range for UA and AA were 2.0 x 10(-6)-1.0 x 10(-4) M and 9.0 x 10(-6)-2.0 x 10(-3) M with detection limits of 5.0 x 10(-7) and 5.0 x 10(-6) M, respectively. Furthermore, metalloporphyrins of other kinds were also used to construct modified electrodes. Their performances were inferior compared with that of the Co(II)TPP modified electrode.

[Pharmacokinetics of hylotelephin in Beagle dogs].

AIM: To investigate the pharmacokinetics of hylotelephin in Beagle dogs and obtain the main pharmacokinetic parameters. METHODS: An HPLC method with UV detection was developed to study the pharmacokinetics of hylotelephin in dogs by joining an internal standard (anthracene). Benzoyl chloride was used to the pre-column derivatization of hylotelephin and methanol-water (64:36) was used as the mobile phase. According to the 3P97 pharmacokinetic program, the main parameters were calculated. RESULTS: The hylotelephin pharmacokinetics conforms to a two-compartment open model after a single iv dose of hylotelephin 10.6 or 21.3 mg x kg(-1) in Beagle dogs. The parameters of two groups were as follows: T(1/2) alpha were 2.3 and 2.1 min, T(1/2) beta were 1.9 and 2.0 h, K12 were 0. 12 and 0.11 min, K21 were 0.17 and 0.21 min, K10 were 0.011 and 0.0094 min, Vc were 0.54 and 0.54 L x kg(-1), AUC were 1.8 and 4.1 g x min x L(-1), CL were 0.0048 and 0.0056 L x kg(-1) x min(-1), MRT were 2.10 and 2.4 h, respectively. CONCLUSION: The pharmacokinetics of hylotelephin after iv administration showed a rapid distribution and elimination process in Beagle dogs and was of first order kinetics.

Nonintubated video-assisted thoracoscopic surgery for management of indeterminate pulmonary nodules.

Indeterminate pulmonary nodules are common findings in clinical practice, especially after widespread use of high-resolution computed tomographic scans for cancer screening. To determine whether the nodule is malignant or not, surgery is usually required for either diagnostic or therapeutic purposes in the early stages. Current development in minimally invasive surgery and anesthesia using video-assisted thoracoscopic surgery without tracheal intubation (nonintubated VATS) are feasible and safe for resection of peripheral lung nodules, including nonintubated needlescopic or uniportal approaches. In addition, nonintubated VATS may offer high-risk patients for intubated general anesthesia opportunities to receive surgery. Therefore, nonintubated VATS can provide an attractive alternative for early diagnosis and treatment of indeterminate lung nodules.

Effects on respiration of nonintubated anesthesia in thoracoscopic surgery under spontaneous ventilation.

Thoracoscopic surgery without tracheal intubation [nonintubated video-assisted thoracoscopic surgery (VATS)] is an emerging treatment modality for a wide variety of thoracic procedures. By surgically induced open pneumothorax, the operated lung collapse progressively while the dependent lung is responsible for sufficiency of respiratory function, including oxygenation and ventilation. Encouraging results showed that ventilatory changes and oxygenation could be adequately maintained in major lung resection surgery and in patients with impaired respiratory function. In spite of a relative hypoventilation, mild hypercapnia is inevitable but clinically well tolerated. An understanding the respiratory physiology during surgical pneumothorax, either in awake or sedative status, and an established protocol for conversion into tracheal intubation are essential for patient safety during nonintubated VATS.

Nonintubated thoracoscopic lobectomy for lung cancer using epidural anesthesia and intercostal blockade: a retrospective cohort study of 238 cases.

Intubated general anesthesia with single-lung ventilation has been considered mandatory for thoracoscopic lobectomy for nonsmall cell lung cancer. Few reports of thoracoscopic lobectomy without tracheal intubation are published, using either thoracic epidural anesthesia (TEA) or intercostal blockade. The comparisons of perioperative outcomes of nonintubated thoracoscopic lobectomy using epidural anesthesia and intercostal blockade are not reported previously. From September 2009 to August 2014, a total of 238 patients with lung cancer who underwent nonintubated thoracoscopic lobectomy were recruited from our prospectively maintained database of all patients undergoing nonintubated thoracoscopic surgery using TEA or intercostal blockade. A multiple regression analysis, adjusting for preoperative variables, was performed to compare the perioperative outcomes of the 2 anesthesia methods. Overall, 130 patients underwent nonintubated thoracoscopic lobectomy using epidural anesthesia whereas 108 had intercostal blockade. The 2 groups were similar in demographic data, except for sex, preoperative lung function, physical status classification, and history of smoking. After adjustment for the preoperative variables, nonintubated thoracoscopic lobectomy using intercostal blockade was associated with shorter durations of anesthetic induction and surgery (P < 0.001). Furthermore, hemodynamics were more stable with less use of vasoactive drugs (odds ratio: 0.53; 95% confidence interval [CI], 0.27 to 1.04; P = 0.064) and less blood loss (mean difference: -55.2 mL; 95% CI, -93 to -17.3; P = 0.004). Postoperatively, the 2 groups had comparable incidences of complications. Patients in the intercostal blockade group had a shorter average duration of chest tube drainage (P = 0.064) but a similar average length of hospital stay (P = 0.569). Conversion to tracheal intubation was required in 13 patients (5.5%), and no in-hospital mortality occurred in either group. Nonintubated thoracoscopic lobectomy using either epidural anesthesia or intercostal blockade is feasible and safe. Intercostal blockade is a simpler alternative to epidural anesthesia for nonintubated thoracoscopic lobectomy in selected patients with lung cancer.

Coronary vasodilatory response to a novel peptide, adrenomedullin 2.

1. Adrenomedullin-2 (AM2) is a novel peptide originally found in a fish and it is structurally related to mammalian AM or fish AM1. Cloning of AM2 cDNA in the mouse, rat and human has been successful. In the present study, the vasodilatory effect of synthetic human AM2 was analysed in isolated artery ring preparations of porcine. 2. Vasodilatory effect of AM2 was the most potent in the coronary artery, followed by the carotid and supramesenteric arteries, but absent in the femoral, pulmonary and renal arteries. 3. The effect of AM2 was equipotent with that of human AM/AM1 in these arteries. 4. AM2-induced relaxation was inhibited by human CGRP (8-37), but not by human AM/AM1 (22-52), suggesting that the vasodilatory response to AM2 is mediated through the CGRP1 receptor. 5. AM2 may share the same receptor (complex) with AM/AM1 for the vasorelaxation. This is the first report of the vasodilatory responses to AM2 in isolated vasculature.

Protective effects of asiaticoside on septic lung injury in mice.

Asiaticoside (AS), a major triterpenoid saponin component isolated from Centella asiatica, has been described to exhibit antioxidant and anti-inflammatory activities. The present study aimed to determine the protective effects and the underlying mechanisms of AS on septic lung injury induced by cecal ligation and puncture (CLP). Mice were pretreated with the AS (45 mg/kg) or AS as well as GW9662 at 1h before CLP, the survival, lung injury, inflammatory mediators and signaling molecules, and Peroxisome proliferator-activated receptor-γ (PPAR-γ) were determined 24 h after CLP. The results showed that AS significantly decreased CLP-induced the mortality, lung pathological damage, the infiltration of mononuclear, polymorphonuclear (PMN) leucocytes and total proteins. Moreover, AS inhibited CLP-induced the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB), the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein in lung tissues, and the production of serum tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Interestingly, the expression of PPAR-γ protein in lung tissue was up-regulated by AS. Furthermore, GW9662 (the inhibitor of PPAR-γ) significantly reversed these beneficial effects of AS in septic mice. These findings suggest that AS could effectively protect from septic lung injury induced by CLP and the underlying mechanisms might be related to up-regulation of PPAR-γ expression to some extent, which inhibits MAPKs and NF-κB pathway.

[Effect of ketoconazole on the activity of CYP4503A4 and CYP450 1A2 of hepatic microsomes in healthy adults].

OBJECTIVE: To observe the effect of ketoconazole on the activity of cytochrome P450 (CYP) 1A2 and 3A4 in hepatic microsomes of healthy adults. METHODS: Human hepatic microsomes obtained from healthy adults were randomly divided into control group and ketoconazole-treatment groups at different concentrations. After 15 min of culture, the substrates (testosterone for CYP3A4 and phenacetin for CYP1A2) were added and incubated for another 20 min. The metabolites (6-testosterone and acetaminophen) were then measured with high-performance liquid chromatography (HPLC) to assess the activities of CYP3A4 and 1A2. RESULTS: Significant difference was found between the groups in the quantity of 6-testosterone and the relative activity of CYP3A4 (P<0.05). The IC(50) of ketoconazole for CYP3A4 was 0. 16 mg/L. Both the quantity of 6-testosterone and the relative activity of CYP3A4 were reduced gradually with the increment of ketoconazole concentration. Significant differences were found between the ketoconazole groups and the control group in both the quantity of acetaminophen and the relative activity of CYP1A2 (P<0.05). Ketoconazole at low doses reduced CYP1A2 activity and but increased the activities at high doses (P<0.05). CONCLUSION: In the range of maximum clinical blood concentration, ketoconazole can inhibit the activity of CYP3A4, but not that of CYP1A2, in the hepatic microsomes in healthy adults.

[RNA interference-mediated silencing of cytochrome P450 3A4 gene in CHL-3A4 cells].

OBJECTIVE: To investigate the effect of small hairpin interfering RNA (shRNA) in suppressing cytochrome P450 3A4 (CYP3A4) gene expression in CHL-3A4 cells. METHODS: Three shRNA expression vectors targeting CYP3A4 gene (CYP3A4 I, C YP3A4 II, and CYP3A4 III, respectively) were designed, synthesized and transfected into CHL-3A4 cells via liposomes. The inhibitory effect of shRNA on CYP 3A4 gene expression was detected by Western blotting and RT-PCR, and the effect of shRNA transfection in suppressing cyclophosphamide-induced cytotoxicity was measured using MTT assay. RESULTS: The vector carrying CYP3A4 III shRNA significantly reduced the expression of CYP3A4 gene at both the mRNA (75%) and protein levels (80%) in CHL3A4 cells. The cytotoxicity of cyclophosphamide was markedly inhibited by CYP3A4 III-mediated suppression of CYP3A4 gene expression by 75% in CHL-3A4 cells. CONCLUSION: The vector-mediated RNA interference can suppress CYP3A4 gene expression in CHL-3A4 cells, and RNA interference technique provides a new means for studying cytochrome P450 gene function in mammalian cells.