Pomalidomide sensitizes lung cancer cells to TRAIL/CDDP-induced apoptosis via directly targeting electron transfer flavoprotein alpha subunit.

Immunomodulatory drugs (IMiDs) represented by thalidomide exhibit benefits when combined with other chemotherapeutic drugs for patients with lung cancer, which inspired the exploration of combining pomalidomide with another agent to treat lung cancer as it is more potent than thalidomide. However, the drugs that can be combined with pomalidomide to benefit patients and related mechanisms remain unclear. Here, we performed a proteomic analysis based on the streptavidin pull-down to identify the potential target of pomalidomide in non-small cell lung cancer (NSCLC). In this work, electron transfer flavoprotein alpha subunit (ETFA), an important enzyme involved in electron transport in the respiratory chains was identified as a crucial cellular target of pomalidomide in NCI-H460 cells. Using apoptosis model and combination analyses, we found that pomalidomide directly targeted ETFA, and increased ATP generation, thereby significantly promoting tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Specific knockdown of ETFA could effectively eliminate the promoting effect of pomalidomide on energy production. Furthermore, respiratory chain inhibitors can effectively block cell apoptosis induced by TRAIL and pomalidomide. These results suggested that pomalidomide may promote apoptosis by facilitating energy production by targeting ETFA and thus enhanced the anticancer effects of chemotherapeutic drugs. It is noteworthy that pomalidomide noticeably increased the anticancer efficacy of cisplatin (CDDP) in NCI-H460 xenograft model with the main mechanisms by inducing apoptosis. Collectively, our data not only provide new insights into the anticancer mechanisms of pomalidomide but also reflect translational prospects of combining pomalidomide with CDDP for NSCLC treatment.

Genes Selectively Expressed in Rat Organs.

Background: Understanding organic functions at a molecular level is important for scientists to unveil the disease mechanism and to develop diagnostic or therapeutic methods. Aims: The present study tried to find genes selectively expressed in 11 rat organs, including the adrenal gland, brain, colon, duodenum, heart, ileum, kidney, liver, lung, spleen, and stomach. Materials and Methods: Three normal male Sprague-Dawley (SD) rats were anesthetized, their organs mentioned above were harvested, and RNA in the fresh organs was extracted. Purified RNA was reversely transcribed and sequenced using the Solexa high-throughput sequencing technique. The abundance of a gene was measured by the expected value of fragments per kilobase of transcript sequence per million base pairs sequenced (FPKM). Genes in organs with the highest expression level were sought out and compared with their median value in organs. If a gene in the highest expressed organ was significantly different (p < 0.05) from that in the medianly expressed organ, accompanied by q value < 0.05, and accounted for more than 70% of the total abundance, the gene was assumed as the selective gene in the organ. Results & Discussion: The Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) pathways were enriched by the highest expressed genes. Based on the criterion, 1,406 selective genes were screened out, 1,283 of which were described in the gene bank and 123 of which were waiting to be described. KEGG and GO pathways in the organs were partly confirmed by the known understandings and a good portion of the pathways needed further investigation. Conclusion: The novel selective genes and organic functional pathways are useful for scientists to unveil the mechanisms of the organs at the molecular level, and the selective genes' products are candidate disease markers for organs.

Endovascular Treatment Versus Best Medical Management in Acute Basilar Artery Occlusion Strokes: Results From the ATTENTION Multicenter Registry.

BACKGROUND: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO). METHODS: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT. We performed an inversed probability of treatment weighting analysis. Qualifying patients had to present within 24 hours of estimated BAO. The primary clinical outcome was favorable functional outcome (modified Rankin Scale score, 0-3) at 90 days. We also performed a sensitivity analysis with the propensity score matching-based and the instrumental variable-based analysis. RESULTS: In our primary analysis using the inversed probability of treatment weighting-based analysis, there was a significantly higher rate of favorable outcome at 90 days among EVT patients compared with BMM-treated patients (adjusted relative risk, 1.42 [95% CI, 1.19-1.65]; absolute risk difference, 11.8% [95% CI, 6.9-16.7]). The mortality was significantly lower (adjusted relative risk, 0.78 [95% CI, 0.69-0.88]; absolute risk difference, -10.3% [95% CI, -15.8 to -4.9]) in patients undergoing EVT. Results were generally consistent across the secondary end points. Similar associations were seen in the propensity score matching-based and instrumental variable-based analysis. CONCLUSIONS: In this real-world study, EVT was associated with significantly better functional outcomes and survival at 90 days. Well-designed randomized studies comparing EVT with BMM in the acute BAO are needed. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2000041117.

A safe and simple exposure and Pringle maneuver in laparoscopic anatomical liver resection of segment 7.

BACKGROUND: Laparoscopic access to liver segment 7 (S7) is difficult for deep surgical situations and bleeding control. Herein, our proposed laparoscopic technique for S7 lesions using a self-designed tube method is introduced. METHODS: Clinical data of patients who underwent laparoscopic anatomical liver resection of S7 (LALR-S7) with the help of our self-designed tube to improve the exposure of S7 and bleeding control in the Second Affiliated Hospital, Third Military Medical University (Army Medical University) from April 2019 to December 2021 were retrospectively analyzed to evaluate feasibility and safety. RESULTS: Nineteen patients were retrospectively reviewed. The mean age was 51.3 ± 10.3 years; mean operation time, 194.5 ± 22.7 min; median blood loss, 160.0 ml (150.0-205.0 ml); and median length of hospital stay, 8.0 days (7.0-9.0 days). There was no case conversion to open surgery. Postoperative pathology revealed all cases of hepatocellular carcinoma (HCC). Free surgical margins were achieved in all patients. No major postoperative complications were observed. Patients with postoperative complications recovered after conservative treatment. During outpatient follow-up examination, no other abnormality was presented. All patients survived without tumor recurrence. CONCLUSIONS: The preliminary clinical effect of our method was safe, reproducible and effective for LALR-S7. Further research is needed due to some limitations of this study.

Chlorogenic acid promotes angiogenesis and attenuates apoptosis following cerebral ischaemia-reperfusion injury by regulating the PI3K-Akt signalling.

CONTEXT: Chlorogenic acid (CGA) has good antioxidant effects, but its explicit mechanism in cerebral ischaemia-reperfusion injury is still uncertain. OBJECTIVE: We studied the effect of CGA in human brain microvascular endothelial cells (HBMECs) under OGD/R damage. MATERIALS AND METHODS: HBMECs in 4 groups were treated with oxygen-glucose deprivation/re-oxygenation (OGD/R) (4 + 24 h), normal no CGA treatment and different concentrations (20, 40 or 80 µM) of CGA. Male C57BL/6J mice were classified as sham, middle cerebral artery occlusion (MCAO), and MCAO + CGA (30 mg/kg/day) groups. Mice in the sham group were not subjected to MCAO. Cell viability, apoptosis, angiogenesis and related protein levels were investigated by CCK-8, flow cytometry, TUNEL staining, tube formation and western blot assays. Infarct volume of brain tissues was analyzed by TTC staining. RESULTS: CGA curbed apoptosis (from 32.87% to 13.12% in flow cytometry; from 34.46% to 17.8% in TUNEL assay) but accelerated cell angiogenesis of HBMECs with OGD/R treatment. Moreover, CGA augmented activation of the PI3K-Akt signalling (p-PI3K/PI3K level, from 0.39 to 0.49; p-Akt/Akt level, from 0.52 to 0.81), and the effect of CGA on apoptosis and angiogenesis was abolished by an inhibitor of PI3K-Akt signalling. Furthermore, CGA attenuated infarct (from 41.26% to 22.21%) and apoptosis and promoted angiogenesis and activation of the PI3K/Akt signalling in MCAO-induced mice. CONCLUSIONS: CGA effectively repressed apoptosis and promoted angiogenesis in OGD/R-treated HBMECs and MCAO-treated mice by modulating PI3K-Akt signalling. Our research provides a theoretical basis for the use of CGA in the treatment of ischaemic stroke.

Sohlh2 alleviates malignancy of EOC cells under hypoxia via inhibiting the HIF1α/CA9 signaling pathway.

Epithelial ovarian cancer (EOC) is the most common and deadly ovarian cancer. Most of the patients have abdominal/pelvic invasion and metastasis at the time of diagnosis, but the underlying mechanism remains unclear. Insufficiency of blood perfusion and diffusion within most solid tumors can lead to a hypoxic tumor microenvironment and promotes tumor malignancy. In the present study, we detected the role of the spermatogenesis- and oogenesis-specific basic helix-loop-helix (bHLH) transcription factor 2 (sohlh2) on migration, invasion and epithelial-mesenchymal transition (EMT) of EOC cell lines under hypoxia in vitro. We also investigated the possible mechanism underlying it. The results showed that sohlh2 inhibited the migration, invasion and EMT of EOC cells and might function through suppression of the hypoxia-inducible factor 1α (HIF1α)/carbonic anhydrase 9 (CA9) signaling pathway. Our results may open a new avenue for the further development of diagnostic tools and novel therapeutics that will benefit EOC patients.

The effect and safety of preoperative biliary drainage in patients with hilar cholangiocarcinoma: an updated meta-analysis.

BACKGROUND: The effect and safety of preoperative biliary drainage (PBD) in patients with perihilar cholangiocarcinoma are still controversial; the aim of our study is to evaluate all aspects of PBD. METHODS: All included studies featured PBD versus non-PBD (NPBD) groups were from 1996 to 2019 and were extracted from Cochrane Library, Embase, PubMed, and Science Citation Index Expanded. RESULTS: Sixteen studies met the inclusion criteria and were included in this analysis. PBD may lead to a significantly higher incidence of overall morbidities (OR 0.67, 95% CI 0.53, 0.85; P = 0.0009) and intraoperative transfusions (OR 0.72, 95% CI 0.55, 0.94; P = 0.02); moreover, bile leakage (OR 0.58, 95% CI 0.24, 1.41; P = 0.04), infection (OR 0.31, 95% CI 0.20, 0.47; P < 0.00001), and cholangitis (OR 0.18, 95% CI 0.007, 0.48; P = 0.0007) are also related to PBD. However, NPBD was associated with more frequent hepatic insufficiency (OR 3.09, 95% CI 1.15, 8.31; P = 0.03). In the subgroup meta-analysis, the differences in the outcomes of bile leakage and overall morbidity lost significance between the PBD and NPBD groups when the mean total serum bilirubin (TSB) concentration was above 15 mg/dl. CONCLUSION: Meta-analysis demonstrated that compared to NPBD, PBD is associated with a greater risk of several kinds of infection and morbidities, but its ability to reduce postoperative hepatic insufficiency cannot be ignored. In patients with a high TSB concentration, PBD tends to be a better choice. However, these results need to be confirmed in a future prospective randomized trial with large samples to clarify the effects and find a specific TSB concentration for PBD.

Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

Anterior Borderzone Angle for Hemodynamic Collateral Metric in Patients with Symptomatic Middle Cerebral Artery Stenosis.

BACKGROUND AND AIMS: We aimed to introduce a parameter of anterior borderzone angle (ABZA) to quantitatively evaluate the ACA-MCA leptomeningeal collaterals for middle cerebral artery stenosis (MCAS). METHODS: Two hundred seventy-five patients with 50-100% MCAS and 100 controls were included. The 95% reference range of ABZA was obtained from the controls. ABZAtrans was defined as "ABZA/the 95% upper limit." Relationships between ABZA and MCAS, -ABZAtrans and the TICI grade, the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grade were analyzed. An ABZA grade model for the ACA leptomeningeal collaterals was tentatively developed. RESULTS: The 95% reference range of ABZA was 0.0º-23.0º. ABZA was significantly associated with MCAS by a function of the fourth power (R2 = 0.723, p < 0.001), and could predict hemodynamic MCAS (≥70%) with an AUC of 0.928 (95% CI 0.903-0.953). ABZAtrans was negatively correlated with the TICI grade (rho = -0.752, p < 0.001) and positively with the ASITN/SIR grade (rho = 0.921, p < 0.001). The ABZA grade was created by rounding -ABZAtrans to a nearest integer, and was closely associated with the ASITN/SIR grade (rho = 0.894, p < 0.001). CONCLUSIONS: ABZA can be used as a hemodynamic parameter to quantitatively evaluate ACA leptomeningeal collaterals.

A novel alignment-free vector method to cluster protein sequences.

Classification of protein are crucial topics in biology. The number of protein sequences stored in databases increases sharply in the past decade. Traditionally, comparison of protein sequences is usually carried out through multiple sequence alignment methods. However, these methods may be unsuitable for clustering of protein sequences when gene rearrangements occur such as in viral genomes. The computation is also very time-consuming for large datasets with long genomes. In this paper, based on three important biochemical properties of amino acids: the hydropathy index, polar requirement and chemical composition of the side chain, we propose a 24 dimensional feature vector describing the composition of amino acids in protein sequences. Our method not only utilizes the chemical properties of amino acids but also counts on their numbers and positions. The results on beta-globin, mammals, and three virus datasets show that this new tool is fast and accurate for classifying proteins and inferring the phylogeny of organisms.

Virus classification in 60-dimensional protein space.

Due to vast sequence divergence among different viral groups, sequence alignment is not directly applicable to genome-wide comparative analysis of viruses. More and more attention has been paid to alignment-free methods for whole genome comparison and phylogenetic tree reconstruction. Among alignment-free methods, the recently proposed "Natural Vector (NV) representation" has successfully been used to study the phylogeny of multi-segmented viruses based on a 12-dimensional genome space derived from the nucleotide sequence structure. But the preference of proteomes over genomes for the determination of viral phylogeny was not deeply investigated. As the translated products of genes, proteins directly form the shape of viral structure and are vital for all metabolic pathways. In this study, using the NV representation of a protein sequence along with the Hausdorff distance suitable to compare point sets, we construct a 60-dimensional protein space to analyze the evolutionary relationships of 4021 viruses by whole-proteomes in the current NCBI Reference Sequence Database (RefSeq). We also take advantage of the previously developed natural graphical representation to recover viral phylogeny. Our results demonstrate that the proposed method is efficient and accurate for classifying viruses. The accuracy rates of our predictions such as for Baltimore II viruses are as high as 95.9% for family labels, 95.7% for subfamily labels and 96.5% for genus labels. Finally, we discover that proteomes lead to better viral classification when reliable protein sequences are abundant. In other cases, the accuracy rates using proteomes are still comparable to that of genomes.

Reduced endothelial progenitor cells in extracranial arterial stenosis but not intracranial arterial stenosis.

OBJECTIVE: Endothelial progenitor cells (EPCs) are novel markers of endothelial dysfunction and are related to cardiovascular disease. However, their relationship with cerebral atherosclerosis (CA) has not been investigated extensively. We aim to study the relationship between CA severity and EPC subpopulations levels. METHODS: We enrolled 197 patients in this study. EPCs were measured by flow cytometry. Digital subtraction angiography was used to assess CA. Arterial lesion severity was evaluated among cerebral arteries which showed steno-occlusion change and the extent of that condition. RESULTS: There was a significant inverse correlation between EPCs level and CA prevalence after adjusting for confounders (CD45(-/dim)CD34(+)CD309(+) cells: odds ratio [OR], 0.110; 95% confidence interval [CI], 0.026-0.475; P = .00; CD45(-/dim)CD133(+)CD309(+) cells: OR, 0.134; 95% CI, 0.030-0.599; P = .01; CD45(-/dim) CD34(+)CD133(+)CD309(+) cells: OR, 0.010; 95% CI, 0.001-0 .541, P = .02). Multivariate logistic regression analysis showed that only the EPCs level was significantly inversely associated with extracranial atherosclerosis rather than intracranial atherosclerosis (P > .05). CONCLUSIONS: Our data indicated that EPCs subpopulations were independent predictors for CA severity, even after controlling for traditional risk factors.

Variant recurrent risk among stroke patients with different CYP2C19 phenotypes and treated with clopidogrel.

Polymorphisms of CYP2C19 have been associated with variant risk of subsequent cardiovascular events in survivors of myocardial infarction (MI) receiving clopidogrel. This study evaluated the impacts of CYP2C19 polymorphisms on stroke recurrence and other vascular events in a cohort of Chinese patients receiving clopidogrel. From Nanjing Stroke Registry Program, 625 consecutive patients with ischemic stroke were enrolled between May 2008 and April 2010. CYP2C19 variants (*2, *3, and *17) were genotyped. Clinical outcomes were determined with three monthly follow-up. The primary endpoint was a composite of vascular death, non-fatal ischemic stroke, and non-fatal MI. The second endpoint was bleeding events. The median exposure to clopidogrel was 13.2 (interquartile range, 8.9-18.0) months. Primary endpoint was observed in 85 (13.6%) patients and secondary endpoint in 13 (2.1%) patients. Frequencies of CYP2C19*1, *2, *3, and *17 alleles were 61.2, 34.0, 3.8, and 1.0%, respectively, in this patient cohort. CYP2C19 loss-of-function allele (*2 and *3, LOF) carriers were observed with higher risk of subsequent vascular events compared with non-carriers (17.2 versus 8.1%, HR = 2.16, 95% CI: 1.31-3.56, p = 0.003). After adjusted for age, sex, major cardiovascular risk factors, and drug agent, CYP2C19 LOF carrier was independently associated with primary endpoint (HR = 2.31, 95% CI: 1.39-3.84, p = 0.001). No significant association between CYP2C19 gain-of-function (*17, GOF) and clinical events was detected. In Chinese stroke survivors treated with clopidogrel, carriers of CYP2C19 LOF allele may have increased risk of recurrence.

C1-almost periodic solutions of BAM neural networks with time-varying delays on time scales.

On a new type of almost periodic time scales, a class of BAM neural networks is considered. By employing a fixed point theorem and differential inequality techniques, some sufficient conditions ensuring the existence and global exponential stability of C1-almost periodic solutions for this class of networks with time-varying delays are established. Two examples are given to show the effectiveness of the proposed method and results.

Learning curve for intracranial angioplasty and stenting in single center.

OBJECTIVE: To identify the specific caseload to overcome learning curve effect based on data from consecutive patients treated with Intracranial Angioplasty and Stenting (IAS) in our center. BACKGROUND: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke and Intracranial Stenosis trial was prematurely terminated owing to the high rate of periprocedural complications in the endovascular arm. To date, there are no data available for determining the essential caseload sufficient to overcome the learning effect and perform IAS with an acceptable level of complications. METHODS: Between March 2004 and May 2012, 188 consecutive patients with 194 lesions who underwent IAS were analyzed retrospectively. The outcome variables used to assess the learning curve were periprocedural complications (included transient ischemic attack, ischemic stroke, vessel rupture, cerebral hyperperfusion syndrome, and vessel perforation). Multivariable logistic regression analysis was employed to illustrate the existence of learning curve effect on IAS. A risk-adjusted cumulative sum chart was performed to identify the specific caseload to overcome learning curve effect. RESULTS: The overall rate of 30-days periprocedural complications was 12.4% (24/194). After adjusting for case-mix, multivariate logistic regression analysis showed that operator experience was an independent predictor for periprocedural complications. The learning curve of IAS to overcome complications in a risk-adjusted manner was 21 cases. CONCLUSIONS: Operator's level of experience significantly affected the outcome of IAS. Moreover, we observed that the amount of experience sufficient for performing IAS in our center was 21 cases.

Ethylene glycol adjusted nanorod hematite film for active photoelectrochemical water splitting.

We reported a facile adjusted method for the synthesis of high surface area nanorod hematite film as a photoanode for application in water splitting. Crystalline hematite nanorods (EG-α-Fe2O3) are fabricated by electrodeposition in Fe(2+) precursor solution with the addition of ethylene glycol (EG) and followed by annealing at 450 °C. The nanorod hematite film fabricated by the modified electrodeposition approach exhibits a more uncompact structure than α-Fe2O3 obtained by directly electrodepositing on the FTO substrate. The optical and structural characteristics of the obtained film are also tested. The results infer that EG can tune the morphology of hematite and improve the photoabsorption in the visible light region due to its inducement of one-dimensional growth of crystal hematite. It also enhances the photoresponse activity of hematite in water splitting by improving the activities at the semiconductor/solution interface. The photocurrent density of EG-α-Fe2O3 nanorods increased to 0.24 mA cm(-2) at 1.4 V vs. RHE in 1 M KOH (pH = 13.6), almost 5 times higher than the original α-Fe2O3 (0.05 mA cm(-2), measured under the same conditions).

Presence of anterior temporal artery associates with good outcome in acute atherosclerotic M1-middle cerebral artery occlusion.

INTRODUCTION: We aim to investigate the correlation between presence of anterior temporal artery (ATA), the first major branch of middle cerebral artery (MCA), on conventional angiography and clinical outcome in patients with acute atherosclerotic M1-MCA occlusion. METHODS: Consecutive patients with acute atherosclerotic M1-MCA occlusion from Nanjing Stroke Registry Program (NSRP) between January 2007 and December 2012 were included in this study. All patients underwent MRI followed by conventional angiography. From their data, we analyzed baseline characteristics, infarction patterns, DWI-ASPECTS, and collateral circulation. The correlation of ATA presence and good clinical outcome, modified Rankin Scale (mRS) score ≤ 2, at 3 months was also calculated. RESULTS: In 98 patients meeting entry criteria, the presence of ATA was found in 44 patients. Patients with ATA present were found to have less hypertension (p = 0.042), lower baseline National Institutes of Health Stroke Scale (NIHSS) (p = 0.043), more small infarcts in perforating artery territory (p = 0.013), and a higher number of DWI-ASPECTS ≥ 7 (p = 0.034). Binary logistic regression analysis showed an adjusted odds ratio of 4.45 for a good outcome in patients with ATA presence (95% CI 1.52 to 13.03, p = 0.007). CONCLUSION: The presence of ATA can be used as a predictor of good outcome in patients with acute atherosclerotic M1-MCA occlusion.

Safety and efficacy of simultaneous bilateral carotid angioplasty and stenting.

In this study, we aimed to evaluate the safety and feasibility of simultaneous bilateral carotid artery stenting (BCAS) compared with staged BCAS in patients with bilateral atherosclerotic carotid stenosis (BCS). From January 2004 to March 2012, 68 patients who underwent BCAS were identified from the Nanjing Stroke Registry Program. Of these patients, 42 (61.8 %) underwent simultaneous BCAS (simultaneous group), and 26 (38.2 %) underwent staged BCAS (staged group). We compared demographic data, major vascular risk factors, procedural parameters, and 30 day outcomes between the simultaneous and staged groups. No significant differences were detected in baseline data between the groups. Patients in the simultaneous group had a lower post-operative systolic pressure compared with the staged group (119.1 ± 16.1 vs. 130.2 ± 17.5 mmHg, P = 0.009). Technical success was 100 % of patients in the simultaneous group and 98.1 % in the staged group. Hemodynamic depression was observed in 57.4 % of procedures, with no significant difference between groups in the rate of HD. Four (5.9 %) patients had neurological complications within 30 days, including two cases of hyperperfusion syndrome in the simultaneous group, and two ischemic events in the staged group. There was no significant difference in the 30 day complication rate between the simultaneous and staged groups (4.8 vs. 7.7 %, P = 0.633). Simultaneous BCAS may be safe and feasible for most patients with BCS, with a similar 30 day complication rate to staged BCAS. Multicenter randomized control studies with larger sample sizes are warranted to further explore the safety and efficacy of simultaneous BCAS.

Argatroban for preventing occlusion and restenosis after extracranial artery stenting.

BACKGROUND/AIMS: Restenosis following extracranial artery stenting is a limitation that affects long-term outcomes. Effective and satisfying pharmacological strategies in preventing restenosis have not been established. This study aimed to evaluate whether argatroban, a direct thrombin inhibitor, could reduce the risk of in-stent restenosis after extracranial artery stenting. METHODS: One hundred and fourteen patients hospitalized between August 2010 and August 2011 were enrolled. Patients were randomly assigned to argatroban (n = 58) and blank control groups (n = 56). The patients in the argatroban arm were treated with 10 mg of intravenous argatroban twice daily 2 days before and 3 days after the stenting procedures. Patients were followed for 12 months after the procedure. During follow-up, restenosis and target revascularization were analyzed. Recurrent cerebrovascular and cardiovascular events and deaths were also compared between the groups. RESULTS: One patient in the stenting group withdrew immediately after the procedure due to unsuccessful stenting. Restenosis occurred in 4 patients (7.4%) in the argatroban group and in 11 patients (21.6%) in the control group during the 6- to 9-month angiographic follow-up period (p = 0.032). Nine months after the procedures, argatroban-treated patients had a trend towards a lower incidence of target revascularization compared with the controls (5.4 vs. 13.7%, p = 0.188). No major bleeding events or other adverse events occurred in the argatroban group. CONCLUSION: This pilot clinical trial is the first that uses argatroban to prevent restenosis in ischemic cerebrovascular disease, and suggests that intravenous administration of argatroban is effective and safe in preventing restenosis after extracranial artery stenting. Larger randomized controlled clinical trials are warranted.

[Predictors of internal borderzone infarcts in atherosclerotic middle cerebral artery stenosis].

OBJECTIVE: To explore the independent predictors of internal borderzone (IBZ) infarcts in patients with atherosclerotic middle cerebral artery stenosis/occlusion (MCAS). METHODS: A total of 167 hospitalized patients with atherosclerotic MCAS during January 2008 and March 2014 were retrospectively analyzed. They were divided into "with IBZ group" (n = 55) and "without IBZ group" (n = 112) according to the findings of magnetic resonance images (MRI). Their clinical data were collected including demographics, traditional vascular risk factors, stenotic degree of MCA and other cerebral supply arteries, TICI grading for antegrade blood flow, ASITN/SIR grading for collateral circulation and other variables. The intra-group data were compared by univariate analysis. Variables with P < 0.1 were included into multivariate Logistic regression model for obtaining the independent predictors of IBZ. Two models were established including either TICI-grading or stenotic degree of MCAS due to close correlations between two variables. RESULTS: There were 45 females and 122 males with a mean age of 54 ± 12 years. Variables with a P value <0.1 in univariate analysis included relatively low blood pressure (P = 0.006), stenotic degree of MCAS (P = 0.012), TICI-grading (P = 0.003), history of hypertension (P = 0.055) and ASITN-grading (P = 0.067). In multivariate model I, independent predictors of IBZ included TICI-grading (OR 4.310, 95%CI 1.698-10.869, P = 0.002), history of hypertension (OR 0.458, 95%CI 0.224-0.936, P = 0.032), relatively low blood pressure (OR 3.848; 95%CI 1.345-7.983, P = 0.039). In multivariate model II, independent predictors of IBZ included stenotic degree of MCAS (P = 0.006; severe vs moderate: OR 4.796, 95%CI 1.676-13.729, P = 0.003; occlusion vs moderate: OR 5.537, 95%CI 1.846-16.603, P = 0.002). The two models had a similar area under the curve (AUC) of receiver operating curve (ROC) of 0.702 (95%CI 0.618~0.787, P < 0.001) and 0.709 (95%CI 0.626-0.792, P < 0.001). CONCLUSION: Severe stenosis or total occlusion of MCA, impairment of antegrade blood flow and relatively low blood pressure are the independent risk factors of IBZ. And history of hypertension is a protective fact or of IBZ in patients with MCAS.