Brain metastases are common in oncologic patients. Stereotactic radiosurgery (SRS) is an effective treatment for oligo brain metastases. However, SRS is not suitable for large metastatic lesions. Fractionated stereotactic radiation therapy (FSRT) is a new option for the treatment of brain metastases. It can deliver high doses of radiation to tumor while protecting the normal tissues and organs outside the irradiation field as much as possible and maintaining good local control rate of tumors. This article reviews the dose-response relationship and adverse reactions of FSRT with different fractionated dose schemes, and the progress of FSRT combined with targeted therapy and immunotherapy.

Animals ; Extremities ; blood supply ; Heparin ; pharmacology ; Male ; Mesentery ; blood supply ; Microcirculation ; drug effects ; Rats ; Rats, Wistar ; Reperfusion Injury ; Splanchnic Circulation ; drug effects

BACKGROUNDClinical observations have shown that the complex fractionated atrial electrogram (CFAE) associates with ganglionated plexus activity in the cardiac autonomic nervous system. This study aimed to investigate the impact of CFAE ablation on vagal modulation to atria and vulnerability to develop atrial fibrillation (AF).

METHODSTen adult mongrel dogs were involved. Cervical sympathovagal trunks were decentralized and sympathetic effects were blocked. CFAE was color tagged on the atrial 3-dimensional image and ablated during AF induced by S1S2 programmed stimulation plus sympathovagal trunk stimulation. Atrial effective refractory period (ERP) and vulnerability window (VW) of AF were measured on baseline and at vagal stimulation at 4 atrium sites. Serial tissue sections from ablative and control specimens received hematoxylin and eosin staining for microscopic examination.

RESULTSMost CFAE areas were localized at the right superior pulmonary quadrant, distal coronary sinus (CS(d)) quadrant, and proximal coronary sinus (CS(p)) quadrant (21.74%, separately). Sinus rhythm cycle length (SCL) shortening did not decrease significantly after ablation at the sites, including right atrial appendage, left atrial appendage, CS(d), and CS(p) (P > 0.05). ERP shortening during vagal stimulation significantly decreased after ablation (P < 0.01); the VW to vagal stimulation significantly decreased after ablation (P < 0.05). The architecture of individual ganglia altered after ablation.

CONCLUSIONSCFAE has an autonomic basis in dogs. The decreased SCL and ERP shortening to vagal stimulation after CFAE ablation demonstrate that CFAE ablation attenuates vagal modulation to the atria, thereby suppressing AF mediated by enhanced vagal activity. CFAE ablation could suppress AF mediated by enhanced vagal activity.

Animals ; Atrial Fibrillation ; therapy ; Autonomic Nervous System ; Catheter Ablation ; methods ; Dogs ; Electrophysiologic Techniques, Cardiac ; methods ; Electrophysiology ; Female ; Male

OBJECTIVETo compare the outcomes of intracytoplasmic sperm injection (ICSI) with retrieved epididymal and testicular sperm for obstructive azoospermia and with ejaculated sperm for severe oligozoospermia and asthenospermia.

METHODSWe retrospectively analyzed 431 ICSI cycles, which were divided according to sperm sources into Groups A (n=287 in patients with severe oligozoospermia or asthenospermia using ejaculated sperm), B (n=109 in obstructive azoospermia patients with sperm retrieved by percutaneous epididymal sperm aspiration, PESA) and C (n=35 in obstructive azoospermia patients with sperm retrieved by testicular sperm extraction, TESE). Comparisons were made among the three groups in the rates of embryo implantation, fertilization, pregnancy, cleavage, and miscarriage.

RESULTSGroup A showed statistically significant differences from Groups B and C in the rates of embryo implantation and pregnancy (18.46% vs. 25.23% and 28.76%, 31.23% vs. 42.16% and 39.39%, P < 0.05). But no significant differences were seen in the rates of fertilization, cleavage and miscarriage among the three groups (P > 0.05).

CONCLUSIONThe rates of embryo implantation and clinical pregnancy are higher in patients with obstructive azoospermia than in those with severe oligozoospermia or asthenospermia after ICSI with ejaculated sperm.

Azoospermia ; therapy ; Epididymis ; cytology ; physiopathology ; Female ; Humans ; Male ; Oligospermia ; therapy ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies ; Sperm Injections, Intracytoplasmic ; methods ; Spermatozoa ; Testis ; cytology ; physiopathology

OBJECTIVETo assess the associations between schizophrenia and six functional genes: dopamine D2 receptor gene (DRD2), dopamine D4 receptor gene (DRD4), 5-hydroxytryptamine 2A receptor gene (5-HT2A), 5-HT6 receptor gene (5-HT6), catechol-O-methyltransferase gene (COMT) and dopamine transporter gene (DAT1).

METHODSWith the techniques of Amp-RFLP and Amp-FLP, association analysis was made between schizophrenia and the six genes in 67 schizophrenic patients from Chinese Han population.

RESULTS(1) Neither genotypes nor alleles of DRD2, 5-HT2A, 5-HT6 and COMT gene showed significant differences between patients and controls (P>0.05). (2) Six repeats (6R) in DRD4 gene, the allele of 480 bp and the genotype of 480/520 in DAT1 gene were found to be of significant differences between the two groups (P<0.05). (3) Only one negative association was observed between the 480 bp allele of DAT1 gene and schizophrenia (OR=0.441, 95% CI:0.202-0.963, Z=2.05, P<0.05).

CONCLUSIONThe 480 bp allele of DAT1 gene is negatively associated with schizophrenia in Chinese Han population, which stands for the dopamine hypothesis of schizophrenia.

Adult ; Alleles ; Catechol O-Methyltransferase ; genetics ; DNA ; genetics ; Dopamine Plasma Membrane Transport Proteins ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Membrane Glycoproteins ; Membrane Transport Proteins ; genetics ; Middle Aged ; Nerve Tissue Proteins ; Polymorphism, Restriction Fragment Length ; Receptor, Serotonin, 5-HT2A ; Receptors, Dopamine D2 ; genetics ; Receptors, Dopamine D4 ; Receptors, Serotonin ; genetics ; Schizophrenia ; genetics

OBJECTIVEElectrical restitution was believed to be a determinant responsible for the stability of heart rhythm. Although numerous studies focused on the role of action potential duration restitution (APDR) in the initiation and maintenance of ventricular fibrillation (VF), the relationship between atrial APDR and atrial fibrillation (AF) has not been fully understood. This study aims to investigate the characteristics of APDR of left atrium (LA) and right atrium (Rs) in canines and the relevance to induction of AF.

METHODSMonophasic action potential (MAP) was recorded from LA and RA in 14 canines using the MAP recording-pacing combination catheter. APDR, plotted as action potential duration (APD) on the preceding diastolic interval (DI), was assessed by use of programmed stimulation with a single extrastimulus (S1S2) at LA and RA. Episodes of AF were recorded and analyzed.

RESULTSAPD90 was significantly shorter in the LA than that in the RA [(157.4 +/- 43.5) ms vs. (170.9 +/- 37.9) ms, P < 0.05]. The mean slope of the APDR curve by S1S2 in the LA was significantly greater than that in the RA (1.3 +/- 0.4 vs. 0.9 +/- 0.3, P < 0.05). The incidence of induced AF was significantly higher in the LA than in the RA (11/18 vs. 7/18, P < 0.05).

CONCLUSIONSThe APDR and MAP characteristics are not uniform between atrium, which may be one of the important mechanisms responsible for the initiation of AF. Heterogeneity of APDR between LA and RA might create critical gradients or a dispersion of repolarization and substrate for re-entrant arrhythmias and vulnerability to AF.

Action Potentials ; Animals ; Atrial Fibrillation ; etiology ; physiopathology ; Atrial Function, Left ; physiology ; Atrial Function, Right ; physiology ; Cardiac Pacing, Artificial ; Dogs ; Electric Countershock

AIMTo probe into the affection and significance of NO on the expression of P-selectin in renal injury following hind limb ischemia/reperfusion in rats.

METHODSIn accordance with the conventional approaches of our department, the model rats were prepared after they were made to undergo 4 hours or ischemia followed by 4 hours of reperfusion of hind limbs. The Wistar rats were divided into four groups randomly: Control group, LI/R group, L-Arg group and L-NAME group. And then in those four groups of Wistar rats, a series of values of measurement were determined such as: Plasma concentrations of nitric oxide (NO), blood urea nitrogen (BUN) and creatinine (Cr). Furthermore, biochemically there came to the assessment of the values including myeloperoxidase (MPO), NO, total nitric oxide synthase (tNOS), inducible NOS (iNOS) and constitutive NOS (cNOS) of renal tissue in different groups. By the methods of electrophoresis and biochemistry, the urine protein was mensurated. The immunohistochemical method was used to detect the expression of P-selectin protein. The morphologic changes were observed with a microscope.

RESULTSAfter hind limbs had suffered from ischemia/reperfusion for 4 hours, there was the occurrence of a series of results such as in the following which were based on the comparison between plasm of LI/R group and control group. The values of NO, BUN and Cr increased significantly, and the trend of indexes such as NO in renal tissue was similar to that in plasma. The values of MPO, tNOS and iNOS in renal tissue all increased significantly after reperfusion, while cNOS decreased distinctly. The urine protein appeared, especially large molecular weight protein. Renal pathology revealed that after LI/R there were edema and infiltration of polymorphonuclear neutrophil (PMN). Immunohistochemically, the expression of P-selectin was upregulated significantly. Compared with LI/R rats, all injury changes were alleviated in L-Arg group. Morphologic changes were mild. Both the content of urine protein and the percentage of apoptosis cell decreased. The expression of P-selectin was downregulated. In L-NAME group, all injury changes got worse. Immunohistochemical results showed strong positive staining of P-selectin.

CONCLUSIONThe renal injury after LI/R may relate to the strong expression of P-selectin. NO may have protective affection by decreasing the expression of P-selectin and alleviating the adhesion, aggregation and infiltration of neutrophils.

Animals ; Kidney ; metabolism ; pathology ; Male ; NG-Nitroarginine Methyl Ester ; adverse effects ; Nitric Oxide ; blood ; P-Selectin ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; pathology

OBJECTIVEThe aim of this study was to investigate the efficiency and safety of ibutilide for cardioversion of persistent atrial fibrillation (AF) during radiofrequency ablation.

METHODSEighteen patients (16 males) with persistent atrial fibrillation were enrolled in this study. All patients underwent circumferential pulmonary vein ablation guided by a Carto three-dimensional mapping system. In addition, linear ablation at the top of the left atrium and the isthmus of mitral valves and complex fractionated atrial electrogram (CAFE) ablation were performed. All patients were still in either atrial fibrillation or atrial flutter after ablation, the patients were treated with 1 mg intravenous ibutilide injection within 10 minutes after unsuccessful ablation. Intravenous injection was stopped in case of sinus rhythm (SR) restoration or occurrence of severe adverse reactions such as ventricular tachycardia. Cardioversion rate within 30 min and adverse reactions within 4 h were observed. Patients were divided into either conversion group or non-conversion group according to whether AF was converted to sinus rhythm within 30 minutes after injection.

RESULTSEleven patients (61.11%) converted to SR after ibutilide injection. There were no significant differences in gender, age, body mass index, left atrium and left ventricular function between conversion group and non-conversion groups. The average conversion time was (13.80 ± 7.64) min, left atrium scar area ratio was significantly larger in non-conversion group (12.40 ± 11.03)% than in conversion group (5.12 ± 3.83)%, P < 0.05. Ibutilide significantly prolonged the average wavelength of the AF wave (171.8 ± 29.5) ms vs. (242.0 ± 40.0) ms at baseline, P < 0.01. The QT interval at 30 min after ibutilide injection (0.39 ± 0.21) s was significantly longer than before injection (0.51 ± 0.08) s, P < 0.05. There was no serious arrhythmias or other adverse reactions post ibutilide injection.

CONCLUSIONSIbutilide is highly effective and safe agent for cardioversion in patients underwent unsuccessful ablation. Left atrium scar area ratio is an important determinant for the conversion rate in this cohort.

Adult ; Aged ; Anti-Arrhythmia Agents ; therapeutic use ; Atrial Fibrillation ; surgery ; Catheter Ablation ; methods ; Female ; Humans ; Male ; Middle Aged ; Sulfonamides ; therapeutic use

OBJECTIVETo explore the effects of down-regulated tryptase expression in mast cells on the synthesis and release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) of vascular endothelial cells.

METHODSTryptase-siRNA (small-interfering RNA) vector was constructed to inhibit tryptase expression in P815 cells. The medium of P815 cells treated by the tryptase-siRNA (RNAi-P815 group) or pure vector (P815 group) was collected and used to culture bEnd.3 cells. The messenger RNAs (mRNAs) of IL-6 and TNF-alpha in bEnd.3 cells and their protein levels in the medium were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively.

RESULTSIL-6 and TNF-alpha mRNAs in bEnd.3 cells cultured in RNAi-P815-conditioned medium decreased significantly compared to those in P815-conditioned medium. Consistently, IL-6 and TNF-alpha protein levels in the medium of bEnd.3 of RNAi-P815 group were lower than those of P815 group.

CONCLUSIONReduced tryptase expression significantly inhibited the synthesis and release of IL-6 and TNF-alpha in vascular endothelial cells. RNA interference targeting tryptase expression may be a new anti-inflammatory strategy for vascular diseases.

Animals ; Cell Line ; Culture Media, Conditioned ; Down-Regulation ; genetics ; Endothelial Cells ; enzymology ; secretion ; Gene Expression Regulation, Enzymologic ; Interleukin-6 ; genetics ; secretion ; Mice ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; Transgenes ; Tryptases ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; secretion

OBJECTIVETo determine the predictive value of HATCH score on recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA).

METHODSThe data of 123 consecutive AF patients (74 paroxysmal and 49 persistent AF) who underwent RFCA between April 2009 and December 2010 in our department were retrospectively analyzed. Of theses patients, 65 (52.9%) patients had HATCH score = 0, 41 (33.3%) patients had HATCH score = 1, and 17 (13.8%) patients had HATCH score ≥ 2 (HATCH = 2 in 11 patients, HATCH = 3 in 5 patients, HATCH = 4 in 1 patient). The recurrence was defined as atrial tachyarrhythmia lasting more than 30 seconds after 3 months post RFCA. The patients were divided into recurrence group and no recurrence group. Relationship between HATCH score and recurrence was observed.

RESULTSThere were 43 cases in recurrence group and 80 cases in no recurrence group. After 12 months follow-up, HATCH score was significant higher in recurrence group than in non-recurrence group [(0.91 ± 0.94) score vs. (0.53 ± 0.80) score, P < 0.05]. The ratio of patients with HATCH ≥ 2 in recurrence group was higher than in non-recurrence group [23.3% (10/43) vs. 8.8% (7/80), P < 0.01]. The sensitivity and specificity of HATCH ≥ 2 to define the risk of recurrence was 25.0%, 92.4% respectively. Cumulative non-recurrence rate of patients with HATCH score ≥ 2 was lower than patients with HATCH score = 0 and 1 (P < 0.05).

CONCLUSIONHigher HATCH score is associated with increased risk of AF recurrence post RFCA.

Aged ; Atrial Fibrillation ; diagnosis ; surgery ; Catheter Ablation ; Female ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Recurrence ; Retrospective Studies ; Treatment Outcome