The Effect of Brief Mindfulness Meditation on Suicidal Ideation, Stress and Sleep Quality.

OBJECTIVES: Suicide is the fourth leading cause of death for individuals aged 15-29 years, and early intervention on suicidal ideation and risk factors should be priortized. Brief mindfulness meditation (BMM) is convenient and cost-effective in improving physical and mental well-being, but less is known about its efficacy for suicidal ideation, stress and sleep quality. We investigated the effects of BMM on suicidal ideation, stress, and sleep quality for individuals with suicide risk. METHODS: Sixty-four college students with high suicidal ideation (aged 18-30 years) were randomly allocated to either a BMM (n = 32) or control group (n = 32). The BMM was based on Anapanasati and core mindfulness concepts. Sixty participants completed all scheduled sessions including pretest, one month of intervention or waiting, and posttest. Suicidal ideation was measured with the Beck Scale for Suicidal Ideation. Stress was evaluated using the Perceived Stress Scale and salivary cortisol levels. Sleep was measured using the Pittsburgh Sleep Quality Index and actigraphy accompanied with 7-day sleep diaries. RESULTS: Post-intervention, the BMM group showed significant decrease in suicidal ideation with a large effect size; the decrease showed a medium effect size in the control group. The BMM group, but not the control group, showed significant decrease in morning salivary cortisol and sleep latency, and improved sleep efficiency. CONCLUSIONS: BMM could help reduce suicidal ideation, stress, and sleep disturbance for individuals with high suicidal ideation and it may implicate effective suicide prevention strategy.

Regional consistency and sample size considerations in a multiregional equivalence trial.

The main objective of a confirmatory multiregional clinical trial (MRCT) is to demonstrate the overall efficacy of test drugs in all participating regions as well as to evaluate the possibility of extrapolating the overall results to each region. With the emergence of the demands of biosimilar drugs development, some guidelines recommended using equivalence design to demonstrate the comparability of efficacy between biosimilar and reference drugs. Previous discussions about assessing regional consistency in MRCT are mainly focused on superiority or non-inferiority designs, while the extensions to equivalence designs were limited. In this work, we proposed a flexible regional consistency criterion for the MRCT with equivalence design. Based on this criterion, sample size determination and sample allocation were also discussed.

Isolation, Chiral-Phase Resolution, and Determination of the Absolute Configurations of a Complete Series of Stereoisomers of a Rearranged Acetophenone with Three Stereocenters.

A synthesis-inspired chemical investigation of the leaves of Melicope ptelefolia led to the isolation of evodialones A-D (1-4), four rearranged acetophenone stereoisomers possessing a prenylated acylcyclopentenone skeleton with three stereogenic carbons. Evodialones C and D (3 and 4) are new minor constituents. The chiral-phase HPLC resolution gave (+)-1-4 and (-)-1-4, eight enantiomers forming a complete stereoisomer library. Their absolute configurations were elucidated via extensive spectroscopic data and a modified Mosher's method. The relationship between the chiral structures and their NMR and ECD data is discussed. Compounds (±)-1, -2, and -4 have significant protective effects on high-glucose-induced oxidative stress in human vein endothelial cells.

Acetophenone derivatives from the roots of Melicope ptelefolia.

Five new prenylated acetophenones, melicoptelins A-E (1-5), along with one known congener (6) were isolated from the roots of Melicope ptelefolia. Among them, compounds 2a/2b, 3a/3b, and 4a/4b were obtained as inseparable interconverting mixtures of keto and enol tautomers. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D, 2D NMR and HRESIMS. Compouds 2a/2b, 4a/4b and 5 exhibit protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC50 values of 34.4, 55.2 and 66.6 µM, respectively.

Synthesis of novel tetrandrine derivatives and their inhibition against NSCLC A549 cells.

A series of novel tetrandrine (Tet) derivatives were synthesized through Suzuki -Miyaura reaction and evaluated for their cytotoxicity against human non-small cell lung carcinoma (NSCLC) A549 cells. Interestingly, most of derivatives showed similar cytotoxicity to Tet against NSCLC A549 cells, and particularly, compounds Y5, Y6, Y9 and Y11 showed the most significant cytotoxic effects with IC50 values ranging from 3.87 to 4.66 mM. The present study is expected to contribute to the future design of more effective anticancer agents in lung cancer chemotherapy.

Online hyphenation of extraction, Sephadex LH-20 column chromatography, and high-speed countercurrent chromatography: A highly efficient strategy for the preparative separation of andrographolide from Andrographis paniculata in a single step.

A novel isolation strategy, online hyphenation of ultrasonic extraction, Sephadex LH-20 column chromatography combined with high-speed countercurrent chromatography, was developed for pure compounds extraction and purification. Andrographolide from Andrographis paniculata was achieved only in a single step purification protocol via the present strategy. The crude powder was ultrasonic extracted and extraction was pumped into Sephadex LH-20 column directly to cut the nontarget fractions followed by the second-dimensional high-speed countercurrent chromatography, hyphenated by a six-port valve equipped at the post-end of Sephadex LH-20 column, for the final purification. The results yielded andrographolide with the amount of 1.02 mg and a purity of 98.5% in a single step, indicating that the present method is effective to harvest target compound from medicinal plant.

Design and synthesis of new tetrandrine derivatives and their antitumor activities.

A series of tetrandrine derivatives were designed and synthesized using Suzuki coupling reaction. Eleven targeted compounds with over 50% inhibition against HL60 and A549 human cancer cell lines at 10 µM were further evaluated for the in vitro antitumor activities by MTT or SRB assay. The biological results revealed that some compounds exhibited potent antitumor activities. Thiophene derivative 6 and acetylphenyl derivative 5 were the most active ones against HL60 and A549 cell lines, with IC50 values less than 5 µM, which thus could be considered as useful candidate for further development of new antitumor agents.

Reporting patterns of adverse drug reactions over recent years in China: analysis from publications.

PURPOSE: The goal of this study was to clarify the reporting patterns of self-reported adverse drug reactions (ADRs) in China. METHODS: A variety of sources were searched, including the official website of China FDA, the national center for ADR monitoring center, publications from PubMed, and so on. We retrieved the relevant information and made descriptive and comparative analysis from the year 2009 to 2013. RESULTS: The ADR reporting numbers were 638,996, 692,904, 852,799, 1,200,000 and 1,317,000 from 2009 to 2013, respectively. Healthcare professionals contributed significantly, and their proportion always exceeded 80% before 2012. The average report per million inhabitants has increased from 479 to 983 from 2009 to 2013. However, the proportion of new or serious report was always below 25%. The reports mainly concern anti-infective agents and traditional Chinese medicine (TCM), especially TCM injection. The proportion of ADR reports in geriatric patients has increased for 4 consecutive years. CONCLUSIONS: ADR report numbers and reporting rates in China are on the rise. However, the proportion of new or serious reports as well as the proportion of reports contributed by consumers and pharmaceutical companies are still quite low. More attention should be paid to the elderly, anti-infective agents and TCM, especially TCM injections.

(±)-Melicolones A and B, rearranged prenylated acetophenone stereoisomers with an unusual 9-oxatricyclo[3.2.1.1(3,8)]nonane core from the leaves of Melicope ptelefolia.

Melicolones A (1) and B (2), a pair of rearranged prenylated acetophenone epimers with an unusual 9-oxatricyclo[3.2.1.1(3,8)]nonane core, were isolated from the leaves of Melicope ptelefolia. Further chiral high-performance liquid chromatography resolution gave enantiomers (+)- and (-)-1, as well as (+)- and (-)-2, respectively. The structures and absolute configurations of the pure enantiomers were determined by extensive spectroscopic data and single crystal X-ray diffraction. All the isolated enantiomers exhibited potent cell protecting activities against high glucose-induced oxidative stress in human vein endothelial cells.

Bioassay-guided preparative separation of angiotensin-converting enzyme inhibitory C-flavone glycosides from Desmodium styracifolium by recycling complexation high-speed counter-current chromatography.

A new strategy of the convergence of high-speed counter-current chromatography (HSCCC) and bioactive assay technique was developed for rapidly screening and separating the angiotensin-converting enzyme (ACE) inhibitors from the aerial parts of Desmodium styracifolium. Bioactivity-guided fractionation of the crude extract was first established to target the bioactive fractions based on HSCCC coupled with in vitro ACE inhibitory assay. Subsequently, the bioactive fractions were further separated by the recycling complexation HSCCC respectively, using 0.10 mol/L copper sulfate in the lower phase of two-phase solvent system composed of n-butanol/water (1:1, v/v). Five C-glycosylflavones, vicenin 2 (1), carlinoside (2), vicenin 1 (3), schaftoside (4) and vicenin 3 (5), were successfully obtained. Their chemical structures were identified using ESI-MS and NMR. All the isolates showed in vitro ACE inhibitory activity with the IC50 values between 33.62 and 58.37 µM. The results demonstrated that the established method was proposed as an excellent strategy to systematically screen and purify active compounds from traditional Chinese medicines.

Adverse drug reactions of spontaneous reports in Shanghai pediatric population.

BACKGROUND: Knowledge of drug safety in the pediatric population of China is limited. This study was designed to evaluate ADRs in children reported to the spontaneous reporting system (SRS) of Shanghai in 2009. METHODOLOGY AND PRINCIPAL FINDINGS: Crude ADR reports submitted to Shanghai SRS in 2009 for individuals aged from birth to 17 years (including 17 years) were included. Data were analyzed with respect to age, gender, category of ADR (System Organ Class [SOC]), the severity of reports and type of reporter. RESULTS: A male overrepresentation was observed regarding the total number of reports. The most frequently reported group of drugs were vaccines (42.15%). Skin rash and fever were the commonest symptoms reported in the total pediatric dataset. The proportion of children that suffered from a serious ADR was 2.16% and that for drug related deaths was 0.34%. And we found that the multiple drug exposure experienced a high proportion of serious ADRs compared with the single drug use (χ²â€Š= 15.99, P<0.0001). Sixty-five percent of ADRs were for children less than 6 years of age. And more than half of reports were from doctors. CONCLUSIONS: In our study, consumers were more likely to report new ADRs though they appear to contribute a relatively small percentage of total reports. We propose that patients would take an active role in reporting ADRs. More researches are needed in order to achieve better understanding the characteristics of ADRs in pediatric population of China.

Exploration of the association rules mining technique for the signal detection of adverse drug events in spontaneous reporting systems.

BACKGROUND: The detection of signals of adverse drug events (ADEs) has increased because of the use of data mining algorithms in spontaneous reporting systems (SRSs). However, different data mining algorithms have different traits and conditions for application. The objective of our study was to explore the application of association rule (AR) mining in ADE signal detection and to compare its performance with that of other algorithms. METHODOLOGY/PRINCIPAL FINDINGS: Monte Carlo simulation was applied to generate drug-ADE reports randomly according to the characteristics of SRS datasets. Thousand simulated datasets were mined by AR and other algorithms. On average, 108,337 reports were generated by the Monte Carlo simulation. Based on the predefined criterion that 10% of the drug-ADE combinations were true signals, with RR equaling to 10, 4.9, 1.5, and 1.2, AR detected, on average, 284 suspected associations with a minimum support of 3 and a minimum lift of 1.2. The area under the receiver operating characteristic (ROC) curve of the AR was 0.788, which was equivalent to that shown for other algorithms. Additionally, AR was applied to reports submitted to the Shanghai SRS in 2009. Five hundred seventy combinations were detected using AR from 24,297 SRS reports, and they were compared with recognized ADEs identified by clinical experts and various other sources. CONCLUSIONS/SIGNIFICANCE: AR appears to be an effective method for ADE signal detection, both in simulated and real SRS datasets. The limitations of this method exposed in our study, i.e., a non-uniform thresholds setting and redundant rules, require further research.

Effect of anti-obesity drug on cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Anti-obesity drugs are widely used to prevent the complications of obesity, however, the effects of anti-obesity drugs on cardiovascular risk factors are unclear at the present time. We carried out a comprehensively systematic review and meta-analysis to assess the effects of anti-obesity drugs on cardiovascular risk factors. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles and proceedings of major meetings for relevant literatures. We included randomized placebo-controlled trials that reported the effects of anti-obesity drugs on cardiovascular risk factors compared to placebo. Overall, orlistat produced a reduction of 2.39 kg (95%CI-3.34 to -1.45) for weight, a reduction of 0.27 mmol/L (95%CI: -0.36 to -0.17) for total cholesterol, a reduction of 0.21 mmol/L (95%CI: -0.30 to -0.12) for LDL, a reduction of 0.12 mmol/L (95%CI: -0.20 to -0.04) for fasting glucose, 1.85 mmHg reduction (95%CI: -3.30 to -0.40) for SBP, and a reduction of 1.49 mmHg (95%CI: -2.39 to -0.58) for DBP. Sibutramine only showed effects on weight loss and triglycerides reduction with statistical significances. Rimonabant was associated with statistically significant effects on weight loss, SBP reduction and DBP reduction. No other significantly different effects were identified between anti-obesity therapy and placebo. CONCLUSION/SIGNIFICANCE: We identified that anti-obesity therapy was associated with a decrease of weight regardless of the type of the drug. Orlistat and rimonabant could lead to an improvement on cardiovascular risk factors. However, Sibutramine may have a direct effect on cardiovascular risk factors.

Change in plasma gelsolin level after traumatic brain injury.

BACKGROUND: Plasma gelsolin depletion has been associated with poor outcome of critically ill patients. However, there is a paucity of data available on circulating plasma gelsolin concentration in traumatic brain injury (TBI). Thus, we sought to investigate change in plasma gelsolin level after TBI and to evaluate its relation with disease outcome. METHODS: Fifty healthy controls and 94 patients with acute severe TBI were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7. Its concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Twenty-six patients (27.7%) died from TBI in a month. After TBI, plasma gelsolin level in patients decreased during the 6-hour period immediately, was at the nadir in 24 hours, increased gradually thereafter, and was substantially lower than that in healthy controls during the 7-day period. A multivariate analysis showed plasma gelsolin level was an independent predictor for 1-month mortality (odds ratio, 0.941; 95% confidence interval, 0.895­ 0.989; p = 0.017) and positively associated with Glasgow Coma Scale (GCS) score (t = 6.538, p 0.001). A receiver operating characteristic curve identified that a baseline plasma gelsolin level 52.7 mg/L predicted 1-month mortality with 88.5% sensitivity and 79.4% specificity (area under the curve, 0.869; 95%confidence interval, 0.783­ 0.930). The predictive value of the gelsolin concentration was thus similar to that of GCS scores (p =0.185). However, gelsolin did not statistically significantly improve the area under the curve of GCS scores (p = 0.517). CONCLUSIONS: Decreased plasma gelsolin level is associated with GCS scores and an independent prognostic marker of mortality after TBI. Reversing plasma gelsolin deficiency may be an effective treatment for TBI.

Effects of combined aspirin and clopidogrel therapy on cardiovascular outcomes: a systematic review and meta-analysis.

BACKGROUND: Aspirin and clopidogrel monotherapies are effective treatments for preventing vascular disease. However, new evidence has emerged regarding the use of combined aspirin and clopidogrel therapy to prevent cardiovascular events. We therefore performed a comprehensive systematic review and meta-analysis to evaluate the benefits and harms of combined aspirin and clopidogrel therapy on major cardiovascular outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings to identify studies to fit our analysis. Eligible studies were randomized controlled trials assessing the effect of combined aspirin and clopidogrel therapy compared with aspirin or clopidogrel monotherapy. We identified 7 trials providing data with a total of 48248 patients. These studies reported 5134 major cardiovascular events, 1626 myocardial infarctions, 1927 strokes, and 1147 major bleeding events. Overall, the addition of aspirin to clopidogrel therapy as compared to single drug therapy resulted in a 9% RR reduction (95%CI, 2 to 17) in major cardiovascular events, 14% RR reduction (95%CI, 3 to 24) in myocardial infarction, 16% RR reduction (95%CI, 1 to 28) in stroke, and 62% RR increase (95%CI, 26 to 108) in major bleeding events. We also present the data as ARR to explore net value as the reduction in cardiovascular events. Overall, we observed that combined therapy yielded 1.06% decrease (95%CI, 0.23% to 1.99%) in major cardiovascular events and 1.23% increase (95%CI, 0.52% to 2.14%) in major bleeding events. CONCLUSION/SIGNIFICANCE: Although the addition of aspirin to clopidogrel resulted in small relative reductions in major cardiovascular events, myocardial infarction, and stroke, it also resulted in a relative increase in major bleeding events. In absolute terms the benefits of combined therapy, a 1.06% reduction in major cardiovascular events, does not outweigh the harms, a 1.23% increase in major bleeding events.

Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis.

BACKGROUND: Folic acid is widely used to lower homocysteine concentrations and prevent adverse cardiovascular outcomes. However, the effect of folic acid on cardiovascular events is not clear at the present time. We carried out a comprehensive systematic review and meta-analysis to assess the effects of folic acid supplementation on cardiovascular outcomes. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. We included randomized placebo-controlled trials that reported on the effects of folic acid on cardiovascular events compared to placebo. Of 1594 identified studies, we included 16 trials reporting data on 44841 patients. These studies reported 8238 major cardiovascular events, 2001 strokes, 2917 myocardial infarctions, and 6314 deaths. Folic acid supplementation as compared to placebo had no effect on major cardiovascular events (RR, 0.98; 95% CI, 0.93-1.04), stroke (RR, 0.89; 95% CI,0.78-1.01), myocardial infarction (RR, 1.00; 95% CI, 0.93-1.07), or deaths from any cause (RR, 1.00;95% CI, 0.96-1.05). Moreover, folic acid as compared to placebo also had no effect on the following secondary outcomes: risk of revascularization (RR, 1.05; 95%CI, 0.95-1.16), acute coronary syndrome (RR, 1.06; 95%CI, 0.97-1.15), cancer (RR, 1.08; 95%CI, 0.98-1.21), vascular death (RR, 0.94; 95%CI,0.88-1.02), or non-vascular death (RR, 1.06; 95%CI, 0.97-1.15). CONCLUSION/SIGNIFICANCE: Folic acid supplementation does not effect on the incidence of major cardiovascular events, stroke, myocardial infarction or all cause mortality.

P16 gene hypermethylation and hepatocellular carcinoma: a systematic review and meta-analysis.

AIM: To quantitatively investigate the effect of p16 hypermethylation on hepatocellular carcinoma (HCC) and hepatocirrhosis using a meta-analysis of available case-control studies. METHODS: Previous studies have primarily evaluated the incidence of p16 hypermethylation in HCC and corresponding control groups, and compared the incidence of p16 hypermethylation in tumor tissues, pericancer liver tissues, normal liver tissues and non-tumor liver tissues with that in other diseases. Data regarding publication information, study characteristics, and incidence of p16 hypermethylation in both groups were collected from these studies and summarized. RESULTS: Fifteen studies, including 744 cases of HCC and 645 non-tumor cases, were identified for meta-analysis. Statistically significant odds ratios (ORs) of p16 hypermethylation were obtained from tumor tissues and non-tumorous liver tissues of HCC patients (OR 7.04, 95% CI: 3.87%-12.78%, P < 0.0001), tumor tissues of HCC patients and healthy liver tissues of patients with other diseases (OR 12.17, 95% CI: 6.64%-22.31%, P < 0.0001), tumor tissues of HCC patients and liver tissues of patients with non-tumorous liver diseases (OR 6.82, 95% CI: 4.31%-10.79%, P < 0.0001), and cirrhotic liver tissues and non-cirrhotic liver tissues (OR 4.96, 95% CI: 1.45%-16.96%, P = 0.01). The pooled analysis showed significantly increased ORs of p16 hypermethylation (OR 6.98, 95% CI: 4.64%-10.49%, P < 0.001) from HCC tissues and cirrhotic tissues. CONCLUSION: P16 hypermethylation induces the inactivation of p16 gene, plays an important role in hepatocarcinogenesis, and is associated with an increased risk of HCC and liver cirrhosis.

Steroids in the treatment of IgA nephropathy to the improvement of renal survival: a systematic review and meta-analysis.

BACKGROUND: Studies have shown that steroids can improve kidney survival and decrease the risk of proteinuria in patients with Immunoglobulin A nephropathy, but the overall benefit of steroids in the treatment of Immunoglobulin A nephropathy remains controversial. The aim of this study was to evaluate the benefits and risks of steroids for renal survival in adults with Immunoglobulin A nephropathy. METHODOLOGY AND PRINCIPAL FINDINGS: We searched the Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE and EMBASE databases. All eligible studies were measuring at least one of the following outcomes: end-stage renal failure, doubling of serum creatinine and urinary protein excretion. Fifteen relevant trials (n = 1542) that met our inclusion criteria were identified. In a pooled analysis, steroid therapy was associated with statistically significant reduction of the risk in end-stage renal failure (RR: 0.46, 95% CI: 0.27 to 0.79), doubling of serum creatinine (RR = 0.34, 95%CI = 0.15 to 0.77) and reduced urinary protein excretion (MD = -0.47 g/day, 95%CI = -0.64 to -0.31). CONCLUSIONS/SIGNIFICANCE: We identified that steroid therapy was associated with a decrease of proteinuria and with a statistically significant reduction of the risk in end-stage renal failure. Moreover, subgroup analysis also suggested that long-term steroid therapy had a higher efficiency than standard and short term therapy.

Should we reoperate for recurrent high-grade astrocytoma?

Despite optimal treatment of post-operative radiotherapy and chemotherapy for newly diagnosed high-grade astrocytoma, nearly all patients eventually recur. However, the efficacy of reoperation for recurrent astrocytoma is still debatable as to different surgical indications. To investigate the therapeutic effect of reoperation on patients with recurrent high-grade astrocytoma more objectively, a retrospective case-matched study was carried out. The clinical data of 63 cases of recurrent high-grade astrocytoma treated between January 2006 and December 2008 were studied. A total of 21 cases received reoperation immediately after tumor recurrence, while 42 cases without reoperation were matched by gender, age, Karnofsky Performance Scale (KPS) score, histopathology, recurrent interval after the first operation, extent of initial surgery, adjuvant treatment and characteristics of recurrent tumor. The study showed that the median survival time was 7 months in the reoperation group, while in non-reoperation group, it was 4 months. There was significant difference on univariate analysis (P < 0.001). Moreover, the median duration time of progression-free survival (PFS) after tumor recurrence was significantly (P < 0.001) longer in the reoperation group (5 months) than that in the non-reoperation group (2.5 months). The prognostic factors of recurrent high-grade astrocytoma included reoperation, KPS score and tumor location. It was indicated that reoperation could prolong the survival time and improve the quality of survival in patients of recurrent high-grade astrocytoma.

In vitro characterization of the angiogenic phenotype and genotype of the endothelia derived from sporadic cerebral cavernous malformations.

BACKGROUND: Cerebral cavernous malformation (CCM) is mainly a disorder of endothelial cells. Although the endothelial function of CCM genes has been characterized in familial CCMs, little attention has been paid to the pathological alterations of the endothelium in sporadic CCMs. OBJECTIVE: We assumed that the endothelia derived from sporadic CCMs present genotypic and/or phenotypic alterations and exhibit unique responses to the pathogenic stimuli. METHODS: Endothelial cells were prepared from fresh operative specimens of sporadic CCMs with a single lesion (CCM-ECs, n = 20). The expression of VEGF and its receptors and CCM1-3 genes were detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Endothelial cell proliferation, migration, sprouting, and tube formation were compared between CCM-ECs and control endothelial cells after different angiogenic stimuli and after silencing CCM1. RESULTS: RT-PCR revealed a highly activated VEGF system in CCM-ECs without significant alteration in CCM1-3 gene expression. Accordingly, CCM-ECs exhibited great growth potential under normal culture conditions and a significantly high proliferation activity in response to various angiogenic stimuli including hypoxia, fetal calf serum, and vascular endothelial growth factor treatment. A considerably higher mobility, spontaneous sprouting and extensive tube-branching were exclusively detected in CCM-ECs. In comparison with control endothelia, CCM-EC resisted apoptotic stimuli and showed distinct responses to activating angiogenesis after silencing CCM1. CONCLUSION: Distinct genotypic and phenotypic features occur in CCM-EC independently from the deficiency in CCM1-3 gene expression. The distinct responses of CCM-EC to different pathogenic stimuli suggest that CCM-EC is a valuable in vitro model for further study of CCMs.