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Objective:To establish the normal reference value of left ventricular function parameters by cadmium-zinc-tellurium (CZT) SPECT stress gated myocardial perfusion imaging (G-MPI) in low-likelihood of stable coronary artery disease (SCAD).Methods:From March 2022 to August 2022, 348 consecutive SCAD patients (146 males, 202 females, age (58±10) years) who underwent exercise or pharmacological stress G-MPI (CZT SPECT) in Beijing Anzhen Hospital, Capital Medical University were retrospectively recruited. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction (LVEF) were acquired using quantitative gated SPECT (QGS) analysis. EDV and ESV were corrected by body surface area (BSA) to obtain EDV index (EDVI) and ESV index (ESVI), respectively. Independent-sample t test, one-way analysis of variance and Mann-Whitney U test were used for data analysis. The influences of EDV, ESV, EDVI, ESVI and LVEF were analyzed by multiple regressions for linear models. Results:There were 314 patients with low-likelihood of SCAD (128 males, 186 females, age (58±10) years) and 34 normal controls (18 males, 16 females, age (55±10) years). There were no significant differences of basic clinical characteristics and left ventricular function parameters in different genders between 2 groups ( z values: from -1.74 to -0.02, t values: from -1.16 to 1.17, all P>0.05). Using the 95% CI as the cut-off value for left ventricular function parameters in patients with a low-likelihood of SCAD, the upper limits of EDV, ESV, EDVI and ESVI in females and males were 84 and 111 ml, 30 and 44 ml, 47 and 54 ml/m 2, 17 and 21 ml/m 2, respectively, and the lower limit of LVEF in females and males were 58% and 55%, respectively. In the low-likelihood of SCAD group, the EDV ((58±13) vs (77±17) ml) and ESV ((16±7) vs (26±9) ml) of females were smaller than those of males ( t values: 10.65, 10.35, both P<0.001), while LVEF of females was higher than that of males ((72±7)% vs (67±6)%; t=-6.23, P<0.001). However, there were no significant differences in left ventricular function parameters among different age groups with the same gender ( F values: 0.12-2.19, all P>0.05). Based on multiple regression for linear models, the primary predictors of EDV, ESV and LVEF were gender and weight ( β values: from -0.380 to 0.358, all P<0.05). Conclusions:Normal reference values of left ventricular function parameters are established by CZT SPECT stress G-MPI in low-likelihood of SCAD patients. Left ventricular EDV and ESV of females are smaller than those of males, while LVEF of females is higher than that of males. The influence of gender on left ventricular function parameters should be considered in clinical practice.
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Objective:To serially characterize the myocardial perfusion, myocardial hibernation and left ventricular (LV) function as well as LV remodeling in progressive coronary artery stenosis in Chinese mini-pigs.Methods:In 8 Chinese mini-pigs (5 males, 3 females; age: 10 months), chronic progression of coronary stenosis and finally occlusion was established using Ameroid constrictor implantation at the 1 cm below the bifurcation of the first diagonal branch of the left anterior descending (LAD) artery. Serial gated 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT, gated 18F-FDG PET/CT imaging and coronary angiography (CAG) were performed before surgery and at the 1st, 4th and 8th week after surgery. Longitudinally, total perfusion defect (TPD), LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), summed motion score (SMS), summed thickening score (STS) and hibernating myocardium (HM) were analyzed. Repeated measures analysis of variance, Kruskal-Wallis rank sum test and Bonferroni correction method were used to analyze data. Results:One mini-pig died of infection after the Ameroid constrictor implantation. In the remaining 7 mini-pigs, TPD was progressively increased with time prolonged (0, 12.0%(0, 33.0%), (41.1±23.7)% and (49.3±24.5)%; H=17.03, P=0.001); Compared with HM before the surgery (100%), HM was gradually reduced from the 1st (21.0%(6.0%, 100%)) to the 4th (18.0%(3.0%, 33.0%)) week after surgery, and then increased to the 8th week after surgery ((23.0±15.4)%; H=13.09, P=0.004), but there was no significant difference between the 1st and 4th week, or between the 4th and 8th week after surgery (both P>0.05 (Bonferroni correction method)). Accordingly, LVEF gradually decreased ((73.7±8.4)%, (63.7±19.1)%, (53.7±14.6)% and (49.9±15.4)%; F=6.22, P=0.004). LVEDV (9.0(6.0, 21.0), (31.4±16.3), (32.9±17.4) and (36.4±17.5) ml; H=8.58, P=0.035)and LVESV ((3.8±3.2), (15.9±15.3), 12.0(10.0, 17.0)and (19.3±10.9) ml; H=10.51, P=0.015) gradually increased. SMS and STS continuously increased as well ( H values: 16.49, 13.33, P values: 0.001, 0.004). Conclusions:With the progression of coronary artery stenosis to occlusion, myocardial perfusion is gradually decreased, while the global and regional LV function, LV remodeling are gradually aggravated, and HM is gradually reduced. After the chronic coronary artery occlusion, myocardial perfusion has a trend to be improved and HM is gradually recovered.
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OBJECTIVE@#To carry out genetic testing and prenatal diagnosis for 29 Chinese pedigrees affected with tuberous sclerosis complex (TSC) and assess efficacy of combined next generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) for the diagnosis.@*METHODS@#NGS and MLPA were used in conjunct to detect variants of TSC1 and TSC2 genes among the probands of the pedigrees. Paternity test was carried out to exclude maternal DNA contamination. Prenatal diagnosis was provided to 14 couples based on the discoveries in the probands.@*RESULTS@#Twenty-seven variants were identified in the TSC1 and TSC2 genes among the 29 pedigrees, which yielded a detection rate of 93.1%. Respectively, 5 (18.5%) and 22 (81.5%) variants were identified in the TSC1 and TSC2 genes. Twelve variants were unreported previously. Prenatal diagnosis showed that five fetuses were affected with TSC, whilst the remaining nine were unaffected.@*CONCLUSION@#Above finding has expanded the spectrum of TSC1 and TSC2 gene variants. Combined NGS and MLPA has enabled diagnosis of TSC with efficiency and accuracy.
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Female , Humans , Pregnancy , DNA Mutational Analysis , Genetic Testing , Mutation , Prenatal Diagnosis , Tuberous Sclerosis/genetics , Tuberous Sclerosis Complex 1 Protein/genetics , Tuberous Sclerosis Complex 2 Protein/geneticsABSTRACT
Objective:To explore the clinical application value and accuracy of cell-free fetal DNA (cff-DNA) technique in prenatal screening.Methods:The results of quantitative fluorescent PCR (QF-PCR) and karyotype of amniotic fluid cells were analyzed retrospectively in 2 398 monocyesis pregnant women who had been amniocentesis at the First Affiliated Hospital of Zhengzhou University from May 2013 to December 2019, and the results of 359 cases who had been examined by single-nucleotide polymorphism array (SNP array).Results:Cff-DNA test of 2, 398 cases indicated 987 cases of trisomy 21, 351 cases of trisomy 18, 135 cases of trisomy 13, 566 cases of sex chromosome abnormality, and 359 cases of other chromosome abnormality. Chromosome karyotype analysis detected 826 cases of trisomy 21, 213 cases of trisomy 18, 17 cases of trisomy 13, 221 cases of sex chromosome abnormality, and 26 cases of other chromosome abnormality. The detection rate were 83.69% (826/987), 60.68% (213/351), 12.59% (17/135), 39.04% (221/566) and 7.24% (26/359), respectively. QF-PCR detected 1 046 cases of trisomy and 188 cases of sex chromosomes abnormality, and the detection rate was 99.05% (1 046/1 056) and 85.07% (188/221), respectively. Compared with the abnormal number detected by chromosome karyotype analysis, 10 cases of trisomeric chimerism and 24 cases of sex chromosome were missed by QF-PCR. Among the 359 other chromosomal abnormalities detected by SNP array, 64 cases were consistent with the results of cff-DNA, and the detection rate was 17.83% (64/359), which was 10.59% higher than the karyotype result.Conclusions:Karyotype analysis is the gold standard for diagnosing chromosomal abnormalities. QF-PCR could diagnose common chromosome aneuploidy rapidly and accurately, and it could be used as an auxiliary detection technique for karyotype analysis. The incidence of sex chromosome chimerism is high, so missed diagnosis should be warned. SNP array could be given priority to verify chromosome microdeletion or microduplication detected by cff-DNA.
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OBJECTIVE@#To explore the genetic basis for a patient with Leydig cell hypoplasia.@*METHODS@#Whole exome sequencing was used to detect genetic variants in the patient. Suspect variants were verified by PCR and Sanger sequencing of the family members.@*RESULTS@#The patient was found to carry two novel variants, namely c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala), of the luteinizing hormone receptor gene (LHCGR), where were respectively inherited from her father and mother. Upon prenatal diagnosis, the fetus was found to be a heterozygous carrier of the c.265A>T (p.Ile189Leu) variant.@*CONCLUSION@#The compound heterozygous variants of c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala) of the LHCGR gene probably underlie the Leydig cell hypoplasia in the patient.
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Objective:To evaluate the clinical value of 18F-fluorodexoyglucose (FDG) PET/CT in distinguishing benign from malignant tumors in patients with cardiac tumors. Methods:Between January 2015 and September 2018, 18F-FDG PET/CT was performed in 3 678 patents in Beijing Anzhen Hospital, and 51 of them (51/3 678, 1.39%) were diagnosed as cardiac tumors. Finally, 28 patients (10 males, 18 females; mean age (52±14) years, age range: 18-84 years) with pathological results were included. According to pathological results, patients were divided into 4 groups: group 1 with primary benign cardiac tumor ( n=9), group 2 with primary malignant cardiac tumor ( n=9), group 3 with lymphoma ( n=6) and group 4 with secondary malignant cardiac tumor ( n=4). All patients underwent early (60 min) 18F-FDG PET/CT imaging and 22 patients (6, 7, 6, 3 patients in group 1, group 2, group 3, group 4 respectively) underwent delayed (120 min) imaging. The maximum standardized uptake value (SUV max) and target/backgroud ratio (TBR) of 4 groups in early imaging and delayed imaging were calculated and compared with one-way analysis of viariace and Scheffe Post-hoc test. TBR were calcualted as SUV max/mean standardized uptake value (SUV mean) in the liver. Receiver operating characteristic (ROC) curve analysis was also performed. Results:SUV max during early imaging, defined SUV max(early), was 2.6±1.5, 9.9±4.0, 20.5±6.1, 9.2±5.8 in group 1-4 respectively ( F=21.39, P<0.01), the value of group 1 was lower than that of group 2 and 3, and the value of group 3 was the highest (all P<0.005). TBR early was 1.1±0.6, 4.1±1.6, 9.4±2.6, 3.7±2.0 in the 4 groups ( F=29.15, P<0.01), the value of group 1 was lower than that of group 2 and 3, and the value of group 3 was the highest (all P<0.005). SUV max in delayed imaging (SUV max(delay)) was 2.4±1.2, 11.0±5.9, 25.8±7.7, 13.7±7.7 respectively in the 4 groups ( F=16.01, P<0.01). TBR delay was also significantly different among the 4 groups (1.3±0.7, 5.5±2.9, 14.4±4.9, 7.9±5.0; F=14.78, P<0.01), the value of group 3 was higher than that of group 1 and 2 (all P<0.05). ROC curve analysis showed optimal cut-off values for indicating malignancy were: SUV max(early)=4.2, TBR early=1.6, SUV max(delay)=4.6, TBR delay=1.9. The corresponding sensitivities, specificities, accuracies were 19/19, 8/9, 96.4%(27/28); 19/19, 7/9, 92.9%(26/28); 16/16, 6/6, 100%(22/22); 16/16, 5/6, 95.5%(21/22), respectively. Conclusions:18F-FDG PET/CT imaging can accurately diagnose malignant cardiac tumors. Delayed imaging can further improve the accuracy for diagnosis of malignant cardiac tumors.
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Objective:To evaluate the image quality (IQ) of 18F-fluorodeoxyglucose (FDG) PET/CT imaging and identify its influenfial factors in diabetes mellitus (DM) and non-DM patients with coronary artery disease (CAD). Methods:A total of 196 consecutive CAD patients (174 males, 22 females, 68 DM; age: (57±10) years) in Beijing Anzhen Hospital between June 2016 and February 2018 were retrospectively analyzed. All patients underwent 18F-FDG myocardial PET/CT imaging. The standardized fasting+ oral glucose loading (OGL) and intravenously injection of insulin protocol was performed. According to the FDG uptake by myocardium, background activity in blood and other visceral organ nearby the heart, the IQ was visually evaluated and scored by 0-4. Zero-two was considered as good IQ, 3-4 was regarded as poor IQ. Patients were divided into three groups: group 1 (non-DM+ good IQ), group 2 (DM+ good IQ), group 3 (DM+ poor IQ). Factors which may affect IQ were analyzed, which including OGL, the injection dose of insulin, fasting blood glucose (FBG), peak blood glucose (PBG), blood glucose (BG) level at 18F-FDG injection (BG injnection), BG increasing rate ((PBG-FBG)/FBG, %), and BG decreasing rate ((PBG-BG injection)/PBG, %). One-way analysis of variance, Spearman correlation analysis and logistic regression analysis were used for data analysis. Results:There were significant differences ( F values: 13.074-38.371, all P<0.05) of FBG, PBG, OGL, BG decreasing rate and the injection dose of insulin among group 1 ( n=132, 67.3%), group 2 ( n=53, 27.1%), group 3 ( n=11, 5.6%). All those parameters, except for OGL, were positively correlated with FDG PET/CT IQ ( r s values: 0.142-0.262, all P<0.05). OGL was negatively correlated with IQ ( r s=-0.324, P<0.05). Logistic regression analysis showed that FBG (odds ratio ( OR)=0.687, 95% CI: 0.633-0.746), PBG( OR=0.786, 95% CI: 0.746~0.829), BG injection( OR=0.631, 95% CI: 0.595-0.716), OGL( OR=0.897, 95% CI: 0.873-0.922), the injection dose of insulin( OR=0.680, 95% CI: 0.618-0.748) were predictive factors (all P<0.01) for good IQ in all patients. For DM patients, OGL was the only predictive factor for good IQ( OR =0.940, 95% CI: 0.904-0.960; P<0.01). Conclusions:FBG, PBG, BG injection, OGL, the injection dose of insulin can predict IQ for all patients with CAD. For DM patients with CAD, OGL is the only predictive factor for good IQ. A good IQ of 18F-FDG PET/CT could be obtained in majority of CAD patients, with the standardized fasting + OGL and intravenously injection of insulin protocol and adjust according to the personal status, and prevent the hypoglycemia from happening.
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Objective To investigate the value of pulmonary ventilation/ perfusion (V/ Q) SPECT in evaluation of anticoagulant therapy for patients with pulmonary embolism (PE) and identify factors which may affect the therapy. Methods From July 2014 to December 2016, sixty-three patients (23 males, 40 females, age (60±14) years), who were clinically diagnosed as PE and underwent V/ Q SPECT before and after anticoagulant therapy, were recruited retrospectively in this study. According to the percentage of lung perfusion defect (PD) out of total lung volume, the patients were divided into mild (<20％) PE, moderate (20％-50％) PE, and severe (>50％) PE groups. The lung PD decreased≥50％ after anticoagulant thera-py and no new PD detected was defined as the standard of effective therapy, otherwise the treatment were defined as ineffective. Data of different groups were compared. Factors that may predict the severity of PD or affect the treatment were analyzed. χ2 test and logistic regression were used for data analysis. Results PE were detected in 476 pulmonary segments and sub segments. The distribution of PE in different lung lobes had no statistically significant difference ( χ2 = 4. 995, P > 0. 05). More pulmonary arterial hypertension (PAH) were detected in patients with severe PE (80％, 12/ 15) and moderate PE (66.7％,16/ 24) in comparison with patients with mild PE (41.7％,10/ 24; χ2 = 7.062, P<0.05). The occurrence of PAH was related to the severity of PD, with odds ratio (OR) value of 2.680 (95％ CI: 1.115-6.446, P<0. 05).PAH was an independent risk factor for treatment effect (OR value: 3.134(95％ CI: 1.341-7. 324), P<0. 05). Conclusions V/ Q SPECT has an important value for evaluating the effect of anticoagulant therapy and guiding individual therapy. The more extent of PE involved, the higher prevalence of PAH. Anticoagu-lant therapy may be ineffective in PE patients with moderate or severe PAH.
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OBJECTIVE:To investigate the effect and cost of Multidimensional iron oral liquid and Polysaccharide iron com-plex capsules in the treatment of iron deficiency anemia during pregnancy. METHODS:By retrospective study,80 cases of iron de-ficiency anemia during pregnancy were divided into control group and trial group in accordance to different therapy plans,with 40 cases in each group. Control group was given Multidimensional iron oral liquid orally,10 ml each time,bid,after breakfast and supper,for consecutive 4 weeks;trial group was given Polysaccharide iron complex capsules orally,0.30 g each time,qd,for con-secutive 4 weeks. Clinical efficacy,erythrocyte related lab indexes,satisfactory rate and ADR were compared between 2 groups, and cost-effectiveness analysis was adopted for economic evaluation. RESULTS:The total effective rate of experimental group was 95.0%,which was higher than 85.0% of control group,but without statistical significance(P>0.05);hemoglobin level,erythro-cyte count and average volume of erythrocyte of trial group were significantly higher or more than control group,and satisfactory rate(95.0% vs. 65.0%)were significantly higher than control group,with statistical significance(P<0.05);no obvious ADR was found in 2 groups. Total cost of trial group and control group were 243.60 and 166.32 yuan,and cost-effective ratio was 2.56 and 1.96;incremental cost-effective ratio was 7.73. Results of sensitivity analysis were same to the result. CONCLUSIONS:Both Multi-dimensional iron oral liquid and Polysaccharide iron complex capsules can improve anemia in patients with iron deficiency anemia during pregnancy. Polysaccharide iron complex capsules show better therapeutic efficacy and satisfactory rate,but it is relatively ex-pensive. Drugs should be selected according to economic situation.
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<p><b>OBJECTIVE</b>To detect potential mutation of F8 gene in a family affected with hemophilia type A.</p><p><b>METHODS</b>Inverse-shifting PCR (IS-PCR), next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and short tandem repeat (STR) assays were used.</p><p><b>RESULTS</b>IS-PCR showed that no inversion of F8 gene has occurred in the family. NGS detected no point mutation or small InDel in the proband, but suggested that the exon 2 of the F8 gene may be deleted. MLPA also showed that exon 2 of the F8 gene was absent in the proband, while the carriers were heterozygous for the deletion, though STR analysis yielded a paradoxical result.</p><p><b>CONCLUSION</b>NGS analysis has identified a large deletion of exon 2 of the F8 gene in a family affected with hemophilia A. Discretion is required when STR analysis was used for carrier screening and antenatal diagnosis. Combination of multiple methods can improve the accuracy for the detection of F8 gene mutations.</p>
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Child , Humans , Male , Exons , Genetics , Factor VIII , Genetics , Genetic Testing , Methods , Hemophilia A , Pedigree , Sequence Deletion , GeneticsABSTRACT
Objective To identify the mutation of trafficking protein particle complex 2 (TRAPPC2) gene in a large Chinese pedigree with X-linked spondyloepiphyseal dysplasia tarda by the PCR-based capillary electrophoresis methods.Methods The blood samples were collected from a large Chinese pedigree of three generations with six affected persons with X-SEDT.Four exons comprising the TRAPPC2 gene open reading frame as well as their exor/intron boundaries were analyzed by argrose electrophoresis and bidirectional direct sequencing of PCR products.Fluorescence labeled fragment analysis was performed by capillary electrophoresis.Results A 5-bp deletion mutation of TRAPPC2 gene in exon 5,c.262_266delGACAT (D88del; I89fX12),was identified in the proband and his unaffected mother(a heterozygote) in the Chinese family with X-SEDT,but no other sequence change occurring in exons 3,4 and 6 was detected.The old sister of proband was determined being carriers because she carries the deletion fragment allele of exon 5 PCR product and the young sister being normal individuals because she carries the wild allele of TRAPPC2 gene.Conclusions The mutation c.262_266delGACAT (D88del; I89fX12) of TRAPPC2 gene was firstly reported in Chinese people.The mutation of c.262_266delGACAT (D88del; I89fX12) in TRAPPC2 gene may be the pathologic cause of the patients in the X-SEDT pedigree.Fragment analysis combined with DNA sequencing by capillary electrophoresis method is effective laboratory test in the small deletion mutation analysis and carriers screening in X-SEDT family.
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Objective To evaluate the efficacy and safety of oral ibuprofen for closure of patent ductus arteriosus (PDA) in preterm infants.Methods The related literatures till December 31st,2011 in Cochrane Library,PubMed,EMBASE,Ovid,Springer,China Academic Journal Full-text Database,Wanfang Database,VIP Database and China Biological Medical Literature Database were searched.The inclusion criteria were:(1) the subject of the research was preterm infants with birth weight less than 2500 g and/or gestational age less than 37 weeks; (2) randomized or semirandomized controlled trial; (3) the intervention group received oral ibuprofen,while the control group received oral placebos / intravenous indomethacin or ibuprofen; (4) the main outcome was the failure rate of PDA closure; (5) hemodynamic changes with PDA were detected by ultrasonography.Meta-analysis was performed by Review Manager 4.22 software.Results Eleven randomized controlled trials were included,among which,three were high quality reports.Meta-analysis showed lower failure rate of PDA closure in subjects received oral ibuprofen than in those received placebos orally (RR =0.22,95 ％ CI:0.14-0.35),while the number of infants required operative closure of PDA decreased significantly (RR =0.16,95％ CI:0.03-0.86).Further analysis showed the effect of oral ibuprofen was similar to intravenous indomethacin (RR =0.93,95 ％ CI:0.57-1.53),but better than intravenous ibuprofen (RR=0.42,95％CI:0.26-0.67).However,oral ibuprofen did not reduced the ratio of patients required operation compared with intravenous indomethacin or ibuprofen (RR=0.58,95％CI:0.24-1.41).The incidence of gastrointestinal hemorrhage was higher in oral ibuprofen group than that in placebos(RR=1.99,95％CI:1.13-3.50).The serum level of creatine was lower in oral ibuprofen group than in intravenous indomethacin or ibuprofen group (weighted average=-19.10,95％ CI:-25.12-12.31).Compared with intravenous indomethcin group,less necrotizing enterocolitis cases were identified in oral ibuprofen group,but no statistical significance was found (RR=0.57,95％ CI:0.30-1.09).No long-term outcome was reported in any selected literature.Conclusions Oral ibuprofen for PDA closure in preterm infants appears to be as effective as intravenous or indomethacin,and more effective than intraveous ibuproten.Oral ibuproten represents better safety.
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Objective To determine the molecular mechanism of berberine (BBR) inhibiting the metastasis and invasion of nasopharyngeal carcinoma 5-8F cells, and identify whether berberine suppresses the tumor-invasive action through inhibiting Ezrin or phosphate-Ezrin. Methods The non-cytotoxic concentration of berberine was detected by MTT assay. Filopodia formation of 5-8F cells was observed by electron microscope. The invasion and motility of 5-8F cells with berberine treatment were measured with Trans-well assay. Western blot was used to investigate the Ezrin and phos-Ezrin expression in 5-8F cells treated by berberine. pcDNA3.1-Ezrin and pcDNA3.1-Ezrin M were transfected into 6-10B cells. The inhibitory effect of berberine on the motility and invasion of 6-10B-pcDNA3.1-Ezrin and 6-10B-pcDNA3.1-Ezrin M was detected, respectively. Results Berberine non-cytotoxic concentration was 0-40 μmol/L. After being treated by berberine, filopodia of 5-8F cells obviously reduced, and the permeating artificial basement membrane cells largely decreased in both time- and concentration-dependent manner. There was significant difference compared with the control group (P<0.05). Berberine suppressed the phos-Ezrin expression of 5-8F cells in both time- and concentration-dependent manner (P<0.05), but the effect of berberine was weaker on 6-10B-pcDNA3.1-Ezrin M than on 6-10B-pcDNA3.1-Ezrin. Conclusion Berberine inhibits nasopharyngeal carcinoma cell invasion through inhibiting phos-Ezrin expression and filopodia formation.