Transjugular Approach to Closure of Patent Foramen Ovale Under the Guidance of Fluoroscopy and Transthoracic Echocardiography: A Case Report.

Background: We describe a rare case of patent foramen ovale (PFO) associated stroke in a patient with pulmonary embolism, inferior vena cava thrombosis and undergoing filter implantation who successfully underwent PFO closure using the right internal jugular venous approach. Case Summary: This is a rare case of a 42-year-old patient who presented with stroke and pulmonary embolism and was diagnosed with a PFO, inferior vena cava thrombosis and underwent filter implantation. The patient suffered from stroke and pulmonary embolism successively; that is, embolic events occurred in both the arterial and venous systems. Transesophageal echocardiography (TEE) showed a PFO with an atrial septal aneurysm (ASA), which we considered a "pathological" PFO. Due to the obstructive nature of the inferior vena cava approach, we successfully performed PFO closure via the right internal jugular venous approach under the guidance of X-ray and transthoracic echocardiography (TTE). Discussion: The right jugular venous approach provides a simple technical solution for patients who require PFO closure when femoral venous access is unavailable, which can be performed under X-ray and TTE guidance.

Fast QLB algorithm and hypothesis tests in logistic model for ophthalmologic bilateral correlated data.

In ophthalmologic or otolaryngologic studies, bilateral correlated data often arise when observations involving paired organs (e.g., eyes, ears) are measured from each subject. Based on Donner's model , in this paper, we focus on investigating the relationship between the disease probability and covariates (such as ages, weights, gender, and so on) via the logistic regression for the analysis of bilateral correlated data. We first propose a new minorization-maximization (MM) algorithm and a fast quadratic lower bound (QLB) algorithm to calculate the maximum likelihood estimates of the vector of regression coefficients, and then develop three large-sample tests (i.e., the likelihood ratio test, Wald test, and score test) to test if covariates have a significant impact on the disease probability. Simulation studies are conducted to evaluate the performance of the proposed fast QLB algorithm and three testing methods. A real ophthalmologic data set in Iran is used to illustrate the proposed methods.

Feasibility of Device Closure for Multiple Atrial Septal Defects With an Inferior Sinus Venosus Defect: Procedural Planning Using Three-Dimensional Printed Models.

BACKGROUND: Multiple atrial septal defects (ASD) with an inferior sinus venosus defect (SVD) have always been considered to be contraindications for interventional therapy. On the basis of early experience using a patent ductus arteriosus (PDA) occluder for interventional treatment for inferior ASD, this study investigated the feasibility of transcatheter closure of multiple ASDs with an inferior SVD under the guidance of three-dimensional (3D) printed heart models. METHODS: Between August 2016 and February 2017, five patients who were diagnosed with multiple ASDs with an inferior SVD at the First Affiliated Hospital of Xi'an Jiaotong University underwent cardiac computed tomography (CT) scans and three-dimensional (3D) echocardiography to generate heart disease models by a 3D printing technique. The best occlusion program was determined through a simulated closure on the model. Percutaneous device closure of multiple ASDs with an inferior SVD was performed following the predetermined program, guided only by fluoroscopy. Follow-up included electrocardiography, transthoracic echocardiography, and transoesophageal echocardiography. RESULTS: Three-dimensional (3D) printed models for all five patients were produced successfully. Four (4) patients had a secundum ASD with an inferior sinus venosus ASD, and one patient had a patent foramen ovale (PFO) with an inferior sinus venosus ASD. All patients were successfully treated with interventional therapy. Inferior sinus venosus ASD was percutaneously closed using the PDA occluder, and the additional secundum ASD or PFO in each patient was percutaneously closed using an ASD or PFO occluder at the same time. There was no device embolisation, procedure-related death or pericardial tamponade. During the 1-year follow-up, a minor residual shunt was detected in one patient. CONCLUSION: The use of 3D printed ASD models provides a useful reference for transcatheter device closure of multiple ASD with an inferior SVD. This approach can provide a new treatment strategy for inferior sinus venosus ASD, which has been considered a contraindication for interventional therapy. However, long-term follow-up in a large number of patients is still warranted.

[Effect of microRNA-133b on Myocardial Fibrosis].

Objective To investigate the effect of microRNA-133b(miR-133b)on cardiac fibrosis and its mechanism.Methods Human cardiac fibroblasts(CFs)were harvested.The proliferation of CFs was detected by CCK8 during the overexpression and knock-down of miR-133b.The expressions of connective tissue growth factor(CTGF),α-smooth muscle actin(α-SMA),collagen Ⅰ,and collagen Ⅲ were detected with qRT-PCR and Western blot analysis after miR-133b overexpression or downexpression.Target genes of miR-133b were predicted by bioinformatics software.Dual-luciferase activity assay were used to verify a target gene of miR-133b.Results qRT-PCR showed that the expression level of miR-133b in the miR-133b mimic group was significantly higher than that in the negative control group(t=26.219,P=0.000).The expression level of miR-133b in the miR-133b inhibitor group was significantly lower than that in the negative control group(t=6.738,P=0.003).After 21,45,69,93,and 117 hours of transfection,the proliferation ability of CFs significantly decreased in the miR-133b mimic group but significantly increased in the miR-133b group(all P<0.05,compared with the negative control group).After overexpression of miR-133b,the mRNA and protein levels of CTGF(t=9.213,P=0.001;t=8.195,P=0.001),α-SMA(t=6.511,P =0.003;t=4.434,P=0.011),collagenⅠ(t=3.172,P=0.034;t=4.053,P=0.015)and collagen Ⅲ(t=6.404,P=0.003;t=5.319,P=0.006)were significantly down-regulated.After the expression of miR-133b was knocked down,the mRNA and protein levels of CTGF(t=9.439,P=0.001;t=14.100,P=0.000),α-SMA(t=4.519,P=0.011;t=4.377,P=0.012),collagen Ⅰ(t=5.966,P=0.004;t=5.514,P=0.005)and collagen Ⅲ(t=4.622,P=0.010;t=4.996,P=0.008)were significantly increased.The relative luciferase activity of the cells co-transfected with miR-133b mimic and WT 3'UTR expression vector was significantly lower than that of the cells co-transfected with mimic control and WT 3'UTR expression vectors(t=5.654,P=0.005);however,there was no significant difference in relative luciferase activity between cells co-transfected with miR-133b mimic and MUT 3'UTR expression vectors and cells co-transfected with mimic control and MUT 3'UTR expression vectors(t=0.380,P=0.724).Conclusion miR-133b may affect the activation and proliferation of CFs by targeting CTGF and thus improve cardiac fibrosis.

Intrahepatic Cholangiocarcinoma Associated Paradoxical Peripheral Embolism and a Submassive Pulmonary Embolism.

Paradoxical peripheral embolism and submassive pulmonary embolism (PE), secondary to cancer-associated thrombosis, are yet to be reported in the literature. Here we describe a case presenting with an acute peripheral arterial embolism. Subsequent testing revealed a PE and an intrahepatic cholangiocarcinoma as the likely risk factors for thrombus, with arterial spread likely achieved through a patent foramen ovale. The patient's symptoms almost relieved upon catheter-directed thrombus fragmentation and aspiration, catheter-directed thrombolysis, and combined anticoagulation. Embolism and major bleeding did not occur during 6 months of follow-up under systemic anticoagulation with rivaroxaban. This case documents that catheter-directed thrombolysis and anticoagulation could be likely effective and safe in the treatment and prevention of recurrence of paradoxical embolism and PE secondary to cancer-associated thrombosis.

Safety of an improved patent ductus arteriosus occluder for transcatheter closure of perimembranous ventricular septal defects with abnormally attached tricuspid chordae tendineae.

BACKGROUND: The off-label use of various devices has been reported for the transcatheter closure of perimembranous ventricular septal defects (PmVSD) because of serious complications, such as heart block and tricuspid regurgitation (TR), associated with conventional ventricular septal defect devices. However, whether certain defects such as PmVSD with abnormally attached tricuspid are fit for interventional treatment is still disputable. AIM: To explore the feasibility and safety of transcatheter closure of PmVSD with abnormally attached tricuspid chordae tendineae using an improved patent ductus arteriosus (PDA) occluder. METHODS: We retrospectively analyzed 20 patients diagnosed with PmVSD with abnormally attached tricuspid chordae tendineae who underwent interventional treatment using an improved PDA occluder at our center from January 2012 to January 2016. Baseline characteristics and procedural and follow-up data were analyzed. RESULTS: All 20 patients achieved procedure success. No heart block occurred during the operation. One patient had a transient complete right bundle branch block within 48 h post-procedure and reverted to normal rhythm after intravenous injections of dexamethasone for 3 d. For all 20 patients, no residual shunt was observed by transthoracic echocardiography post-procedure. During the average follow-up period of 2.4 years, no severe TR was observed. CONCLUSION: Using of the improved PDA occluder for the transcatheter closure of PmVSD with abnormally attached tricuspid chordae tendineae is a safe and promising treatment option. However, long-term follow-up in a large group of patients is still warranted.

Clinical relevance of atrial septal aneurysm and patent foramen ovale with migraine.

AIM: To test the potential association between atrial septal aneurysm (ASA) and migraine in patent foramen ovale (PFO) closure patients through an observational, single-center, case-controlled study. METHODS: We studied a total of 450 migraineurs who had right-to-left shunts and underwent PFO closure in a retrospective single-center non-randomized registry from February 2012 to October 2016 on the condition that they were aged 18-45 years old. Migraine was diagnosed according to the International Classification of Headache Disorders, 3rd edition and evaluated using the Headache Impact Test-6 (HIT-6). All patients underwent preoperative transesophageal echocardiography, contrast transthoracic echocardiography, and computed tomography or magnetic resonance imaging examinations, with subsequent fluoroscopy-guided PFO closure. Based on whether they have ASA or not, the patients were divided into two groups: A (PFO with ASA, n = 80) and B (PFO without ASA, n = 370). Baseline characteristics and procedural and follow-up data were reviewed. RESULTS: Compared to group B, group A had an increased frequency of ischemic lesions (11.3% vs 6.2%, P = 0.038) and migraine with aura (32.5% vs 21.1%, P = 0.040). The PFO size was significantly larger in group A (P = 0.007). There was no significant difference in HIT-6 scores between the two groups before and at the one-year follow-up after the PFO closure [61 (9) vs 63 (9), P = 0.227; 36 (13) vs 36 (10), P = 0.706]. CONCLUSION: Despite its small sample size, our study suggests that the prevalence of ASA in PFO with migraine patients is associated with ischemic stroke, larger PFO size, and migraine with aura.

Transcatheter Closure of Perimembranous Ventricular Septal Defects in Children using a Wire-Drifting Technique.

OBJECTIVE: Explore the feasibility and safety of transcatheter closure of perimembranous ventricular septal defects using a wire-drifting technique (WT) in children. METHODS: We retrospectively analyzed 121 pediatric patients diagnosed with perimembranous ventricular septal defects who underwent interventional treatment at the First Affiliated Hospital of Xi'an Jiaotong University from Dec 2011 to Dec 2014. Based on the method used for arteriovenous loop establishment during the procedure, the patients were divided into a conventional technique (CT) group and a WT group. RESULTS: In total, 51 of the 53 patients (96.2%) in the CT group and 66 of the 68 patients (97.1%) in the WT group achieved procedural success, with no significant difference between the two groups (p>0.05). The CT group showed a nonsignificantly higher one-time success rate of arteriovenous loop establishment (94.3% vs. 91.2%, p>0.05). The procedure time was 46.0 (14.0) min and 46.5 (10.0) min in the CT and WT groups, respectively. The CT procedure was discontinued in the 2 cases (3.8%) of intraprocedural atrioventricular block in the CT group. In the one case (1.9%) of postprocedural atrioventricular block in the CT group, a permanent pacemaker was implanted to resolve third-degree atrioventricular block three months after the procedure. In the WT group, no cases of intraprocedural atrioventricular block occurred, and one case (1.5%) of postprocedural atrioventricular block occurred. In this case, intravenous dexamethasone injection for three days returned the sinus rhythm to normal. Aggravated mild to moderate tricuspid regurgitation was observed in 2 patients (3.8%) in the CT group during the 2-year follow-up period; aggravated tricuspid regurgitation was not observed in the WT group. During the 2-year follow-up period, there was no evidence of residual shunting in either group. CONCLUSION: Transcatheter closure of perimembranous ventricular septal defects with the WT is safe and effective in children.

Transcatheter closure of perimembranous ventricular septal defects in children using a Wire-Drifting Technique

OBJECTIVE: Explore the feasibility and safety of transcatheter closure of perimembranous ventricular septal defects using a wire-drifting technique (WT) in children. METHODS: We retrospectively analyzed 121 pediatric patients diagnosed with perimembranous ventricular septal defects who underwent interventional treatment at the First Affiliated Hospital of Xi'an Jiaotong University from Dec 2011 to Dec 2014. Based on the method used for arteriovenous loop establishment during the procedure, the patients were divided into a conventional technique (CT) group and a WT group. RESULTS: In total, 51 of the 53 patients (96.2%) in the CT group and 66 of the 68 patients (97.1%) in the WT group achieved procedural success, with no significant difference between the two groups (p>0.05). The CT group showed a nonsignificantly higher one-time success rate of arteriovenous loop establishment (94.3% vs. 91.2%, p>0.05). The procedure time was 46.0 (14.0) min and 46.5 (10.0) min in the CT and WT groups, respectively. The CT procedure was discontinued in the 2 cases (3.8%) of intraprocedural atrioventricular block in the CT group. In the one case (1.9%) of postprocedural atrioventricular block in the CT group, a permanent pacemaker was implanted to resolve third-degree atrioventricular block three months after the procedure. In the WT group, no cases of intraprocedural atrioventricular block occurred, and one case (1.5%) of postprocedural atrioventricular block occurred. In this case, intravenous dexamethasone injection for three days returned the sinus rhythm to normal. Aggravated mild to moderate tricuspid regurgitation was observed in 2 patients (3.8%) in the CT group during the 2-year follow-up period; aggravated tricuspid regurgitation was not observed in the WT group. During the 2-year follow-up period, there was no evidence of residual shunting in either group. CONCLUSION: Transcatheter closure of perimembranous ventricular septal defects with the WT is safe and effective in children.

A Case Report on Pulmonary Arteriovenous Fistula with Recurrent Cerebral Infarction.

Patent foramen ovale (PFO) and pulmonary arteriovenous fistula (PAVF) have been both proposed as a mechanism for cerebral infarction. However, there are only a few reports on how to distinguish the role of the two factors in cerebral infarction.

Multidisciplinary assessment of PFO with substantial right-to-left shunting and medium-term follow-up after PFO device closure: A single-center experience.

OBJECTIVES: To describe the multidisciplinary assessment of patent foramen ovale (PFO) with substantial right-to-left shunting (RLS) and medium-term follow-up after PFO closure for stroke or transient ischemic attack (TIA). BACKGROUND: PFO closure is a therapeutic option to prevent recurrent ischemic event in patients with cryptogenic stroke and TIA. The apparent lack of benefit seen in previous studies was in part due to the inclusion of patients with alternate mechanisms of stroke/TIA. However, the long-term follow-up results of RESPECT trial confirmed that PFO closure could reduce the recurrence rate of stroke compared to medical therapy. The obvious difference between RESPECT and the other studies is that RESPECT recruited more relevant patients with substantial RLS. METHODS: From May 2013 to October 2015, all subjects diagnosed as cryptogenic stroke or TIA with substantial RLS who underwent PFO closure at our institution were included. All patients underwent multidisciplinary assessment to exclude stroke/TIA with definite etiology. Baseline characteristics, clinical manifestations, procedural, and follow-up data were reviewed. RESULTS: A total of 219 consecutive patients with substantial RLS undergoing PFO closure were identified. There were no procedure-related deaths, strokes, or TIA. Mean follow-up was 2.0 ± 0.7 years. Early residual shunting was visible in 9 patients (4.1%); however, during follow-up, only 3 patients (1.4%) had residual RLS detected by contrast transthoracic echocardiography (cTTE). The annual risk of recurrent ischemic stroke or TIA was 0.457%. CONCLUSIONS: PFO closure can be performed safely and effectively in patients with cryptogenic stroke or TIA. In selected patients with substantial RLS, following appropriate multidisciplinary assessment, excellent results with low incidence of recurrent events may be achieved.

Bone marrow-derived mesenchymal stem cells modified with IGFBP-3 inhibit the proliferation of pulmonary artery smooth muscle cells.

Pulmonary arterial hypertension (PAH) is a common clinical cardiovascular disease, leading to the excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and endothelial cells, and is associated with a high mortality rate. Recently, stem- and progenitor cell-mediated gene therapies have provided a novel approach for the treatment of PAH. However, the function of human bone marrow-derived mesenchymal stem cells (hBM­MSCs) modified with the insulin-like growth factor binding protein-3 (IGFBP-3) gene in the regulation of PAH is not yet fully understood. In this study, we explored the biological role of IGFBP­3-modified hBM­MSCs in the proliferation of human PASMCs (hPASMCs), and also investigated the potential underlying molecular mechanisms. Our results revealed that IGFBP-3-modified hBM­MSCs inhibited the proliferation of angiotensin II-stimulated hPASMCs following co-culture on cell culture inserts. In addition, total DNA synthesis and the protein levels of hPASMCs in co-culture were decreased. Moreover, the IGFBP­3-modified hBM­MSCs promoted apoptosis and downregulated the expression of B-cell lymphoma-2 (Bcl-2), but increased the expression of Bcl-2 associated X protein (Bax) in hPASMCs. Furthermore, the IGFBP­3-modified hBM­MSCs significantly induced a phenotypic change in the hPASMCs from the synthetic to the contractile phenotype in co-culture. Importantly, the levels of several related proteins in the hPASMCs, including phosphorylated (p-)insulin receptor substrate-1 (p-IRS-1), phosphoinositide 3-kinase (p-PI3K), serine/threonine-protein kinase (p-Akt), mitogen-activated protein kinase (p-p38), p-Jun N-terminal kinase (p-JNK) and extracellular signal-regulated kinase (p-ERK), were markedly decreased by the IGFBP-3-modified hBM­MSCs following co-culture. Taken together, our findings suggest that IGFBP-3-modified hBM­MSCs inhibit the proliferation and promote the apoptosis of hPASMCs, and promote the swithc to a contractile phenotype in more effectively than wild-type hBM­MSCs, possibly through the activation of the PI3K/Akt and Ras-mitogen-activated protein kinase (MAPK) signaling pathways. The findings of our study suggest that IGFBP­3­modified hBM­MSCs may be a promising therapeutic strategy for the treatment of PAH.

Hydroxyethyl starch resuscitation downregulate pro-inflammatory cytokines in the early phase of severe acute pancreatitis: A retrospective study.

In the present study, we investigated the effects of hydroxyethyl starch (HES) 130/0.4 on serum pro-inflammatory variables, immunologic variables, fluid balance (FB)-negative(-) rate and renal function in severe acute pancreatitis (SAP) patients. From October, 2007 to November, 2008, a total of 120 SAP patients were enrolled in this retrospective study. Fifty-nine patients in the HES group received 6% HES 130/0.4 combined with crystalloid solution for fluid resuscitation (HES group). In the control group, 61 patients received only crystalloid solution after admission. Interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-α levels in serum were measured on days 1, 2, 4 and 8. The peripheral blood CD4+CD8+ T lymphocyte rates, serum BUN and Cr values were also measured on days 1, 4 and 8. Patients with FB(-) rates were recorded from day 1 to 8. Interaction term analysis (hospital stay and fluid resuscitation methods) based on mixed-effects regression model revealed significantly lower levels of IL-1 and TNF-α in the HES group compared with the control group. The difference in curve's risk ratio was not significant for IL-6, CD4+CD8+ T lymphocyte rate, BUN and Cr values (P>0.05). In the HES group, we detected a significantly higher rate of patients with FB(-) from day 4 to 8 (P<0.05). Thus, HES 130/0.4 resuscitation could decrease the IL-1 and IL-8 levels, shorten the duration of positive FB, and preserve the patient's immune status as well as renal function during the early phase of SAP.

Implantation of radioactive (125)I seeds improves the prognosis of locally advanced pancreatic cancer patients: A retrospective study.

Locally advanced pancreatic cancer is associated with a very poor prognosis. This study was performed to evaluate whether patients with locally advanced pancreatic cancer benefit from (125)I seed implantation. This retrospective study included 224 patients with locally advanced pancreatic cancer, with 137 patients (61.2%) in the implantation (IP) group and 87 (38.9%) in the non-implantation (NIP) group. The survival status, complications and objective curative effects were compared between the groups. The average operative time in the IP group was significantly longer than that in the NIP group (243±51 vs. 214±77 min). The tumor response rates were 9.5% and 0 at the 2nd month after surgery in the IP and NIP groups, respectively (P<0.05). The IP group exhibited a trend toward pain relief at the 6th month after surgery. The global health status scores of the IP group were higher than those of the NIP group at the 3rd and 6th month after surgery. The median survival time in the IP group was significantly longer than that in the NIP group. In conclusion, patients with locally advanced pancreatic cancer can benefit from (125)I seed implantation in terms of local tumor control, survival time, pain relief and quality of life.

Is there comparable morbidity in pylorus-preserving and pylorus-resecting pancreaticoduodenectomy? A meta-analysis.

Pancreaticoduodenectomy (PD) is the most effective treatment for patients with pancreatic head or periampullary lesions. Two major strategies exist: pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-resecting pancreaticoduodenectomy (PRPD). However, it is yet unclear regarding the morbidity after PPPD and PRPD. This study analyzed the morbidity after PPPD and PRPD to determine the optimal surgical treatment of masses in the pancreatic head or periampullary region. A systematic search of databases identifying randomized controlled trials (RCTs) from the Cochrane Library, PubMed, EMBASE and Web of Science was performed. Outcome was compared by postoperative morbidity including overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding, biliary leakage, ascites and delayed gastric emptying (DGE) rate between PPPD and PRPD. The DGE rate in the PRPD subgroups (conventional PD [CPD] and subtotal stomach-preserving PD [SSPPD], respectively) was also analyzed. The results showed that 9 RCTs including 722 participants were included for meta-analysis. Among these RCTs, 7 manuscripts described PRPD as CPD, and 2 manuscripts described PRPD as SSPPD. There were no significant differences in the overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding, or biliary leakage between PPPD and PRPD. There was a lower rate of DGE with PRPD than that with PPPD (RR=2.15, P=0.03, 95% CI, 1.09-4.23). Further subgroup analysis indicated a comparable DGE rate for the CPD but a lower DGE rate for the SSPPD group than the PPPD group. However, the result did not indicate any difference between CPD and SSPPD regarding the DGE rate (P=0.92). It is suggested that PPPD is comparable to PRPD in overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding and biliary leakage. The current data are not sufficient to draw a conclusion regarding which surgical procedure is associated with a lower postoperative DGE rate. Our conclusions were limited by the available data. Further evaluations of RCTs are needed.

Platypnea-orthodeoxia syndrome in a patient with a pre-existing patent foramen ovale successfully treated with an atrial septal occluder.

Platypnea orthodeoxia syndrome is associated with dyspnea and arterial oxygen desaturation accentuated by an upright posture. It can be secondary to an intracardiac shunt. We report a case of platypnea-orthodeoxia syndrome (POS) in a 58-year old male patient who had a pre-existing patent foramen ovale (PFO) and substantial pulmonary pathologies. He was successfully treated by percutaneous transcatheter closure of the PFO. Our case highlights the importance of recognition of this rare syndrome in patients who present with unexplained hypoxia for whom transcatheter closure of the interatrial shunt can be safely carried out.

Isolation and characterization of LIGHT (TNFSF14) gene homologue in zebrafish (Danio rerio).

The tumor necrosis factor superfamily (TNFSF) proteins are cytokines involved in many biological processes. In this study, the TNF superfamily member 14 (TNFSF14, LIGHT) has been isolated from zebrafish Danio rerio (designated zLIGHT). The full-length open reading frame (ORF) of zLIGHT cDNA consists of 708 bp encoding a protein of 235 amino acids. The zLIGHT open reading frame (ORF) genomic sequence consists of three introns and four exons, is about 9.9 kb in size. Real-time quantitative PCR (qPCR) analysis suggested that zLIGHT was predominantly expressed in zebrafish spleen. The soluble LIGHT (zsLIGHT) had been cloned into the pSUMO vector, SDS-PAGE and Western blotting analysis confirmed that the recombinant protein SUMO-zsLIGHT was efficiently expressed in Escherichia coli BL21 (DE3). Laser scanning confocal microscopy analysis showed that SUMO-zsLIGHT could bind to its receptors on T cells. LIGHT is involved in many important biological effects, including up-regulating proinflammatory chemokines, cytokines, inducing cell death, apoptosis, and enhancing T cell survival. Zebrafish may conduct as a model animal for further research on LIGHT.

Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study.

RATIONALE: Although the phosphodiesterase type 5 inhibitors sildenafil and tadalafil have demonstrated efficacy in patients with pulmonary arterial hypertension (PAH), monotherapy with these agents has not been conclusively shown to reduce clinical worsening events. OBJECTIVES: To evaluate the safety and efficacy of the phosphodiesterase type 5 inhibitor vardenafil in Chinese patients with PAH. METHODS: In a randomized, double-blind, placebo-controlled study, 66 patients with PAH were randomized 2:1 to vardenafil (5 mg once daily for 4 wk then 5 mg twice daily; n = 44) or placebo (n = 22) for 12 weeks. Patients completing this phase were then treated with open-label vardenafil (5 mg twice daily) for a further 12 weeks. MEASUREMENTS AND MAIN RESULTS: At Week 12, the mean placebo-corrected 6-minute walking distance was increased with vardenafil (69 m; P < 0.001), and this improvement was maintained for at least 24 weeks. Vardenafil also increased the mean placebo-corrected cardiac index (0.39 L·min(-1)·m(-2); P = 0.005) and decreased mean pulmonary arterial pressure and pulmonary vascular resistance (-5.3 mm Hg, P = 0.047; -4.7 Wood U, P = 0.003; respectively) at Week 12. Four patients in the placebo group (20%) and one in the vardenafil group (2.3%) had clinical worsening events (hazard ratio 0.105; 95% confidence interval, 0.012-0.938; P = 0.044). Vardenafil was associated with only mild and transient adverse events. CONCLUSIONS: Vardenafil is effective and well tolerated in patients with PAH at a dose of 5 mg twice daily.