[Efficacy of fenestrated atrial septal defect occulders on pulmonary hypertension dogs].

Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery. Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.

InP-based deep-ridge NPN transistor laser.

We report an InP-based deep-ridge NPN transistor laser (TL, λ∼1.5 µm). By placing the quantum well (QW) active material above the heavily Zn-doped base layer, both the optical absorption of the heavily p-doped base material and the damage of the quality of the QWs resulted from the Zn diffusion into the QWs are decreased greatly. CW operation of the TL is achieved at -40 °C, which is much better than the shallow-ridge InP-based NPN TL. With future optimization of the growth procedure, significant improvement of the performance of the deep-ridge InP-based NPN TLs is expected.

MicroRNA-15a inhibits inflammatory response and apoptosis after spinal cord injury via targeting STAT3.

OBJECTIVE: To clarify the function of microRNA-15a in the spinal cord injury (SCI) and its potential mechanism. PATIENTS AND METHODS: The plasma levels of microRNA-15a and signal transducer and activator of transcription 3 (STAT3) in SCI patients were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the expressions of microRNA-15a and STAT3 was analyzed. The in vitro SCI model was established in H2O2-induced C8-D1A and C8B4 cells, and in vivo SCI model was established in mice by hitting T10. The mRNA and protein expressions of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) were detected in the SCI model. The apoptosis was examined by flow cytometry or TUNEL staining, respectively. The motor function of mouse hindlimb was evaluated using the Basso Beattie Bresnahan (BBB) standard scale. The target gene of microRNA-15a was predicted by bioinformatics and further verified by dual-luciferase reporter gene assay. The expression changes of target genes in C8-D1A and C8B4 cells with microRNA-15a overexpression or knockdown were examined by qRT-PCR and Western blot. Finally, rescue experiments were performed to evaluate the regulatory effects of microRNA-15a and STAT3 on cell apoptosis. RESULTS: MicroRNA-15a was lowly expressed in plasma of SCI patients, while STAT3 was highly expressed with a negative correlation to microRNA-15a. Identically, microRNA-15a was lowly expressed in H2O2-induced C8-D1A and C8B4 cells, and STAT3 was highly expressed. MicroRNA-15a overexpression downregulated mRNA and protein levels of TNF-α and IL-6 in C8-D1A and C8B4 cells. BBB score was markedly low in SCI mice relative to controls. SCI mice injected with microRNA-15a mimics had higher BBB score than those injected with negative control. Besides, SCI mice with microRNA-15a overexpression had downregulated expressions of STAT3, TNF-α, and IL-6 in the impaired spinal cord tissues, as well as lower apoptotic rate. Through bioinformatics, we found binding sites between STAT3 and microRNA-15a. Their binding conditions were further verified by dual-luciferase reporter gene assay. Moreover, STAT3 expression was negatively regulated by microRNA-15a. Finally, rescue experiments showed that STAT3 overexpression could reverse the regulatory effects of microRNA-15a on expressions of TNF-α and IL-6, as well as apoptosis. CONCLUSIONS: MicroRNA-15a expression decreases in the SCI model, which participates in the process of SCI by regulating inflammatory response and cell apoptosis via targeting STAT3.

Evaluation of a modified antimycobacterial susceptibility test using Middlebrook 7H10 agar containing 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride.

A rapid and accurate antimycobacterial susceptibility test is essential for effective treatment of tuberculosis. The aim of this study was to evaluate a modified method applying 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC) to the Clinical and Laboratory Standards Institute (CLSI) guideline for susceptibility testing of Mycobacterium tuberculosis. A total of 132 clinical isolates of M. tuberculosis, forty-eight isolates showing resistance to one or more of the first-line antituberculosis drugs, and eighty-four fully susceptible isolates were collected from hospitals of a nationwide distribution from June to September 2004. The modified procedure was conducted basically according to the agar-proportion method described in the CLSI Guideline both with STC 50 mug/mL. The amount of growth in each well was recorded and graded at 2nd and 3rd weeks after inoculation. After 3 weeks of incubation, the diagnostic sensitivity and specificity for the detection of drug-resistant strains of STC-containing agar proportion methods were 100%, except ethambutol-low level resistance, of which the diagnostic sensitivity was 93.4%. After two weeks of incubation in STC-containing agar proportion methods, one hundred of the 107 strain-drug combinations have shown drug resistance, indicating the sensitivity of 93.5%. Especially, all 41 isoniazid-resistant strains and 19 of 21 rifampin-resistant strains (90.5%) could be detected after two weeks of incubation. A modification of the agar proportion method using STC resulted in a reliable and more easily interpretable data, and detected most of resistant strains a week earlier than conventional method.

[Receptors of monoamine in sympathetic preganglionic neurons of neonatal rat spinal cord in vitro].

By means of intracellular recordings from spinal cord slices of neonatal rats in vitro, the effects of 5-hydroxytryptamine (5-HT), nor-adrenaline (NA) and adrenaline (AD) on membrane potential in sympathetic preganglionic neurons (SPN) were observed, in order to clarify whether these neuron contain a single type of the monoamine receptor or in combination with more than one type of receptors. The results showed that: (1) 5-HT, NA and AD induced membrane depolarization respectively in 57.1% (16/28), 60% (15/25) and 52.4% (11/21) of SPN. (2) According to the reactions of SPN to the three monoamines, several subtypes of SPN could be divided: those sensitive to all the three monoamines (3/19), those sensitive to two of them (9/19), those only sensitive to one type of monoamines (4/19) and those insensitive at all (3/19). The significance of coexistence of more than one type of the three monoamines in a single neuron remains to be elucidated.

Substance P- and 5-hydroxytryptamine-mediated depolarization in sympathetic ganglion neurons.

By means of intracellular recordings from sympathetic ganglion in vitro, the present study was to investigate whether the receptors of substance P (SP) and 5-hydroxytryptamine (5-HT) exist in the same neuron or separately in different neurons of guinea pig celiac ganglion (CG) and inferior mesenteric ganglion (IMG) and whether there are some interactions between the two transmitters. Of the 133 neurons of CG, 66 (49.6%) responded to both SP and 5-HT, 40 (30.1%) only to SP or 5-HT, 27 (20.3%) insensitive to both. The corresponding numbers of the corresponding groups of neurons of the 129 IMG neurons are 47 (36.4%), 65 (50.4%) and 17 (13.2%). Continuous superfusion of IMG with 5-HT did not affect SP depolarization, while continuous superfusion of IMG with SP did not affect 5-HT depolarization. The results indicate that SP receptor and 5-HT receptor may exist in the same neuron, and neither affects each other.

[The relationship of late slow excitatory potential with 5-hydroxytryptamine and substance P in the guinea-pig celiac ganglion].

The work was carried out to investigate the relationship of non-cholinergic late slow excitatory potential (LS-EPSP) with 5-hydroxytryptamine (5-HT) and substance P (SP) in the neurons of the guinea pig celiac ganglion (CG) using intracellular electrodes in vitro. During repetitive stimulation of the splanchnic nerve (SN), LS-EPSP following a series of action potentials could be recorded in 161 out of 206 neurons (78.2%); Application of 5-HT and SP by superfusion or pressure ejection induced 5-HT depolarization in 102 out of 149 neurons (68.5%) and SP depolarization in 98 out of 188 neurons (52.1%), respectively; Most neurons, from which LS-EPSP could be recorded during stimulation of SN, were sensitive to 5-HT (73/88, 83.0%) and SP (68/114, 59.7%). However, only a small number of neurons not showing LS-EPSP during stimulation of SN were sensitive to 5-HT (10/26, 38.5%, P < 0.0001) and SP (11/36, 30.6%, P < 0.01). The results support the viewpoint that both 5-HT and SP are involved in the formation of LS-EPSP as transmitters; In addition, both effects of 5-HT and SP were examined in 133 neurons. There were 66 of these neurons (49.6%) to be sensitive to both 5-HT and SP, suggesting that there may be some functional relations between 5-HT and SP in the neurons of guinea pig CG.

Knockdown of BAG3 induces epithelial-mesenchymal transition in thyroid cancer cells through ZEB1 activation.

The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial-mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of ß-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis.