Efficacy of repetitive transcranial magnetic stimulation for post-stroke depression: a systematic review and meta-analysis of randomized clinical trials.

We aimed to conduct a meta-analysis to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with post-stroke depression (PSD). Six relevant electronic databases (PubMed, CENTRAL, Embase, Web of Science, CINAHL, and PsycINFO) were searched. Randomized controlled trials (RCTs) that compared rTMS with control condition for PSD were included. The mean change in depression symptom scores was defined as the primary efficacy outcome. Secondary outcomes included the remission rate of depression, stroke recovery, and cognitive function recovery. In total, 7 RCTs with 351 participants were included. At post-treatment, rTMS was significantly more effective than the control condition, with a standardized mean difference (SMD) of -1.15 (95%CI: -1.62 to -0.69; P<0.001, I2=71%) and remission with an odds ratio (OR) of 3.46 (95%CI: 1.68 to 7.12; P<0.001; I2=11%). As for stroke recovery, rTMS was also better than the control condition (SMD=-0.67, 95%CI: -1.02 to -0.32; P<0.001). However, no significant difference was found for cognitive function recovery between the two groups (SMD=4.07, 95%CI: -1.41 to 9.55; P=0.15). To explore the potential moderators for the primary outcome, a series of subgroup and sensitivity analyses were performed. The results implied that rTMS may be more effective in Asian samples than in North American samples (P=0.03). In conclusion, from the current evidence in this study, rTMS could be an effective treatment for patients with PSD. Further clinical studies with larger sample sizes and clearer subgroup definitions are needed to confirm these outcomes.

The optimal immune checkpoint inhibitors combined with chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) plus chemotherapy (CT) have strikingly expanded the therapeutic landscape for advanced non-small cell lung cancer (NSCLC), but little is known about which is superior. We performed a meta-analysis that compared the efficacy and safety of PD-1 inhibitor + CT with PD-L1 inhibitor + CT. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and major international scientific meetings were searched for relevant randomized controlled trials (RCTs), and the indirect analysis was performed for PD-1 + CT vs PD-L1 + CT. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (TRAEs). RESULTS: 8 phase III RCTs with 4253 patients comparing PD-1/PD-L1 + CT in NSCLC were included. The PD-1 + CT led to notably longer OS most in low/negative expression of PD-L1 for NSCLC patients compared with PD-L1 + CT. In terms of Grade 3-5 TRAEs, the results showed that PD-1 + CT and PD-L1 + CT exclusively increased the risk of adverse incidence than CT alone, especially for PD-L1 + CT (p < 0.00001). For subgroups including female, young patients, patients with nonsmoker, and EGFR/ALK wild-type, PD-1 + CT was associated with prolonged OS (p < 0.05). Meanwhile, for no liver metastasis of NSCLC patients, we found obviously OS advantage for patients treated with PD-1 + CT compared to PD-L1 + CT. CONCLUSIONS: ICIs + CT seemed to be more effective first-line regimen and PD-1 + CT could be recommended as the first-rank therapy for advanced NSCLC patients with low/negative expression of PD-L1. However, we should be particularly vigilant about the occurrence of the Grade 3-5 TRAEs.

Efficacy of repetitive transcranial magnetic stimulation for post-stroke depression: a systematic review and meta-analysis of randomized clinical trials

We aimed to conduct a meta-analysis to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with post-stroke depression (PSD). Six relevant electronic databases (PubMed, CENTRAL, Embase, Web of Science, CINAHL, and PsycINFO) were searched. Randomized controlled trials (RCTs) that compared rTMS with control condition for PSD were included. The mean change in depression symptom scores was defined as the primary efficacy outcome. Secondary outcomes included the remission rate of depression, stroke recovery, and cognitive function recovery. In total, 7 RCTs with 351 participants were included. At post-treatment, rTMS was significantly more effective than the control condition, with a standardized mean difference (SMD) of -1.15 (95%CI: -1.62 to -0.69; P<0.001, I2=71%) and remission with an odds ratio (OR) of 3.46 (95%CI: 1.68 to 7.12; P<0.001; I2=11%). As for stroke recovery, rTMS was also better than the control condition (SMD=-0.67, 95%CI: -1.02 to -0.32; P<0.001). However, no significant difference was found for cognitive function recovery between the two groups (SMD=4.07, 95%CI: -1.41 to 9.55; P=0.15). To explore the potential moderators for the primary outcome, a series of subgroup and sensitivity analyses were performed. The results implied that rTMS may be more effective in Asian samples than in North American samples (P=0.03). In conclusion, from the current evidence in this study, rTMS could be an effective treatment for patients with PSD. Further clinical studies with larger sample sizes and clearer subgroup definitions are needed to confirm these outcomes.

Meta-analysis of survival benefit with postoperative chemoradiotherapy in patients of lymph node positive esophageal carcinoma.

BACKGROUND: The effect of postoperative chemoradiotherapy (CRT) for esophageal carcinoma (EC) was investigated. Patients who can obtain benefit from this treatment modality have not yet been well identified. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for studies published from January 1993 to July 2016. Research comparing surgery alone (SA) with postoperative CRT in patients with resectable EC was procured; collected articles were written in English. RESULTS: Nine studies comparing of postoperative CRT versus SA (n = 1650) in patients with resectable EC met the inclusion criteria. No survival benefit was achieved for postoperative CRT compared with SA. Subgroup analysis was conducted for patients under resection with positive lymph node carcinoma; there was a significant survival benefit at 1 year [risk ratio (RR) = 0.55 95% CI: 0.37-0.82; P = 0.003], 3 years (RR = 0.71 95% CI: 0.61-0.83; P<0.0001), as well as 5 years (RR = 0.86 95% CI: 0.78-0.94; P = 0.0007). Subgroup analysis by tumor histology of squamous cell carcinoma (SCC) was also performed, but there was no significant survival benefit when postoperative CRT was compared with SA. Fail models after surgery were performed; the RR for local control rate and distant metastasis rate were 0.64 (95% CI 0.49-0.85; P = 0.002) and 0.87 (95% CI 0.67-1.15; P = 0.34), which indicates lower local recurrence rates of post-CRT than that of SA. CONCLUSION: This meta-analysis demonstrated a survival benefit of postoperative CRT over SA in resectable EC patients with positive lymph nodes. Improvements of local control rates with postoperative CRT were also detected.

Mechanism of hif-1α mediated hypoxia-induced permeability changes in bladder endothelial cells

This study aimed to investigate the mechanism of hypoxia-inducible factor-1 alpha (HIF-1α) mediated hypoxia-induced permeability changes in bladder endothelial cells. Models of in vitro hypoxic cell culture of bladder cancer, bladder cancer cells with low HIF-1α expression and HIF-1α RNA interference (RNAi) expression vector were established. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of HIF-1α and vascular endothelial growth factor (VEGF) in each group. Bladder cell permeability was determined. Results showed that protein and mRNA expression of HIF-1α and VEGF at 3 and 12 h of hypoxia were significantly higher than normal control (P<0.05), and peaked at 12 h. HIF-1α and VEGF expression in the hypoxic group and hypoxic+3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1) group were significantly higher than normal control (P<0.05), while expression in the hypoxic+YC-1 group was significantly lower than the hypoxic group (P<0.05). Bladder cell permeability in the hypoxic and hypoxic+YC-1 group were significantly increased compared to normal control (P<0.05), while in the hypoxic+YC-1 group was significantly decreased compared to the hypoxic group (P<0.05). Most of the cells in the stably transfected HIF-1α RNAi expression vector pcDNA6.2-GW/EmGFP-miR-siHIF-1α expressed green fluorescence protein (GFP) under fluorescence microscope. pcDNA6.2-GW/EmGFP-miR-siHIF-1α could significantly inhibit HIF-1α gene expression (P<0.05). HIF-1α and VEGF expression in the hypoxic group and siHIF-1α hypoxic group were significantly higher than normal group (P<0.05), while expression in the siHIF-1α hypoxic group was significantly lower than the hypoxic group (P<0.05). Findings suggest that HIF-1α is an important factor in the increase of bladder cancer cell permeability.

Mechanism of hif-1α mediated hypoxia-induced permeability changes in bladder endothelial cells.

This study aimed to investigate the mechanism of hypoxia-inducible factor-1 alpha (HIF-1α) mediated hypoxia-induced permeability changes in bladder endothelial cells. Models of in vitro hypoxic cell culture of bladder cancer, bladder cancer cells with low HIF-1α expression and HIF-1α RNA interference (RNAi) expression vector were established. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of HIF-1α and vascular endothelial growth factor (VEGF) in each group. Bladder cell permeability was determined. Results showed that protein and mRNA expression of HIF-1α and VEGF at 3 and 12 h of hypoxia were significantly higher than normal control (P<0.05), and peaked at 12 h. HIF-1α and VEGF expression in the hypoxic group and hypoxic+3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) group were significantly higher than normal control (P<0.05), while expression in the hypoxic+YC-1 group was significantly lower than the hypoxic group (P<0.05). Bladder cell permeability in the hypoxic and hypoxic+YC-1 group were significantly increased compared to normal control (P<0.05), while in the hypoxic+YC-1 group was significantly decreased compared to the hypoxic group (P<0.05). Most of the cells in the stably transfected HIF-1α RNAi expression vector pcDNA6.2-GW/EmGFP-miR-siHIF-1α expressed green fluorescence protein (GFP) under fluorescence microscope. pcDNA6.2-GW/EmGFP-miR-siHIF-1α could significantly inhibit HIF-1α gene expression (P<0.05). HIF-1α and VEGF expression in the hypoxic group and siHIF-1α hypoxic group were significantly higher than normal group (P<0.05), while expression in the siHIF-1α hypoxic group was significantly lower than the hypoxic group (P<0.05). Findings suggest that HIF-1α is an important factor in the increase of bladder cancer cell permeability.

Improved protocol for extracting genomic DNA from frozen formalin-fixed tissue resulting in high-quality whole mtDNA.

Formalin fixation and paraffin embedding is widely used for convenient and long-term storage of tumor tissue and precious sources to perform genetic studies. However, DNA fragmentation is one of the major flaws of genomic DNA isolation from formalin fixation tissues, which limits its further usage. Here, we present an improved method for isolating high-quality genomic DNA from formalin fixation tissue. We obtained high-quality genomic DNA of more than 20 kb from samples frozen for more than 2 years. Furthermore, to verify DNA quality, the whole mitochondrial DNA (mtDNA) genomes from the normal and tumor tissue of the same patient were successfully amplified with two overlapping PCR fragments comprising more than 8379 bp in length for each fragment. In addition, the whole genomes were sequenced with a 48-well based primer panel in order to avoid potential sequencing errors from artificial recombination, which was further confirmed with an mtDNA phylogenetic strategy. Our improved DNA extraction method from formalin fixation tissue and sequencing strategy for entire mtDNA genomes will generate unambiguous sequence analysis results for clinical samples.

Association between PAI-1 polymorphisms and plasma PAI-1 level with sepsis in severely burned patients.

We investigated the association between plasminogen activator inhibitor-1 (PAI-1) polymorphisms and plasma PAI-1 level with sepsis in severely burned patients. A total of 182 patients with burn areas lager than 30% of the body surface area were enrolled in this study. Peripheral blood samples were obtained from 103 patients with sepsis (sepsis group) and 79 patients without sepsis (control group). An allele-specific polymerase chain reaction assay was used to determine PAI-1 polymorphism 4G/5G distribution. Plasma PAI-1 levels were detected using an enzyme-linked immunosorbent assay. The frequency of the 4G/4G genotype and the 4G allele frequency in the sepsis group were 42.7 and 62.1% respectively, which were significantly higher than those in the control group (P < 0.05). Sepsis patients had a significantly higher plasma PAI-1 level than the control group (P < 0.05). Compared with the 5G/5G genotype, PAI-1 concentrations were significantly higher in the 4G/4G genotype (P < 0.05). The study indicates that the 4G/5G promoter polymorphism of PAI-1 gene may be related to the susceptibility to burn sepsis and that the 4G/4G genotype may be an important genetic risk factor of burn sepsis. Additionally, PAI-1 concentrations in the serum are increased in patients with burn sepsis.

Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis.

To study the effect of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) on the rat salpingitis model, 50 female Wistar rats were randomly divided into one control and five model groups. Mixed bacteria were injected into the oviducts of model groups. The treated acute and chronic groups received intraperitoneal injections of WJMSCs (1 x 10(6)) once a week for three weeks. Serum inflammation factor, collagen fiber content and oviduct-specific glycoprotein (OVGP) levels were detected in control, chronic, ex-treatment acute and chronic, and treated acute and chronic groups (N = 5 for each group). Pregnancy rate and litter size of control, chronic, treated acute and treated chronic groups were compared. Serum TNF-α and INF-γ levels increased in ex-treatment acute and chronic groups, and restored to normal in the acute treated group but not in the treated chronic group. Oviduct collagen fibers did not increase significantly before or after treatment in the acute group, but it increased in the ex-treatment chronic group and did not improve after treatment. After treatment, OVGP levels restored to normal in the acute group but reduced in the ex-treatment and treated chronic groups and chronic group. The pregnancy rate and litter size of the treated acute group recovered to normal, but in the treated chronic group and chronic model group, they decreased significantly. Thus, intraperitoneal injection of WJMSCs could recover the function of the oviduct in acute salpingitis rats, but its effect on chronic salpingitis was poor. Timely treatment of salpingitis is crucial to preserve reproductive function.

Safety of recombinant human granulocyte-macrophage colony-stimulating factor in healing pediatric severe burns.

We explored the safety of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for healing burns in children. Subjects were randomly assigned to two groups: the experimental group received external rhGM-CSF gel, and the control group received rhGM-CSF gel matrix components, applied to the burn surface. Neither group was given any other drugs that promote wound healing. Each day we recorded the pulse, body temperature, and respiration status in the two groups. We detected the blood routine, urine routine, and hepatic and renal function before the patients received drug treatment and after 72 h. The wound scab and healing states in the two groups were recorded every 4 days to evaluate wound healing rate and time taken for complete healing. Adverse reactions and their rate of occurrence were also recorded. The median time of healing was 15 days in the experimental group and 19 days in the control group (log-rank χ(2) = 5.139, P < 0.05). After 10 days, the experimental group healing rate was consistently higher than that of the control group (significantly different using intuitive analysis), suggesting the experimental group method was more effective. There were no obvious adverse reactions. There was no significant difference between the blood routine, urine routine, and liver and kidney function in the two groups before the treatment and after 3 days (P > 0.05). Compared with saline treatment of severe burns, rhGM-CSF can effectively shorten the healing time without significant adverse reactions, and is an effective and safe treatment for burns in children.

Roles of peripheral B1 cells in the individualized treatment of adult idiopathic thrombocytopenic purpura.

We aimed to explore the changes of peripheral B1 cells before and after treatment of adult idiopathic thrombocytopenic purpura (ITP) and to investigate the association of these changes with the disease condition and prognosis. Ninety-seven ITP patients were divided into the effective or ineffective groups, based on their response to hormone therapy. Forty healthy volunteers were enrolled into the control group (HC). The percentages of CD19+ cells, B1 cells, and platelet-associated immunoglobulin (PAIg) in peripheral blood from healthy volunteers and ITP patients before and after treatment were evaluated, and blood platelet (PLT) counts were determined. The percentages of CD19+ cells [(21 ± 10.0) vs (11.2 ± 7.1)%], B1 cells [(8.85 ± 5.23) vs (2.2 ± 1.3)%], and PAIg [(28 ± 19) vs (11.7 ± 8)%] in whole blood from ITP patients before treatment were significantly higher than those in whole blood from healthy controls (P < 0.05). Before treatment, the percentage of B1 cells and PAIg in ITP patients was negatively correlated with the PLT level (r = -0.89, P < 0.05 and r = -0.814, P < 0.05, respectively). Further, the B1 cell percentage was positively associated with the PAIg percentage in ITP patients before treatment. In the effective group, the B1 cell percentage was reduced sharply at 1 month after treatment [(2.45 ± 1.75) vs (8.74 ± 5.04)%, P < 0.05)], so as at 3 and 6 months. However, in the ineffective group, there was no difference in the B1 cell percentage before and after treatment [(7.9 ± 5.6) vs (8.76 ± 5.26)%]. This obvious association of changes in peripheral B1 cells with disease condition and prognosis in ITP patients may be of certain clinical significance for guiding the individualized treatment of ITP.

Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism

Our aim was to investigate the role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism. Coronary angiography and intravascular ultrasound (IVUS) were performed in 60 stable angina pectoris (SAP) patients and 60 unstable angina pectoris (UAP) patients. The chemotactic activity of monocytes in the 2 groups of patients was examined in Transwell chambers. High-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), regulated on activation in normal T-cell expressed and secreted (RANTES), and fractalkine in serum were examined with ELISA kits, and expression of MCP-1, RANTES, and fractalkine mRNA was examined with real-time PCR. In the SAP group, 92 plaques were detected with IVUS. In the UAP group, 96 plaques were detected with IVUS. The plaques in the UAP group were mainly lipid 51.04% (49/96) and the plaques in the SAP group were mainly fibrous 52.17% (48/92). Compared with the SAP group, the plaque burden and vascular remodeling index in the UAP group were significantly greater than in the SAP group (P<0.01). Chemotactic activity and the number of mobile monocytes in the UAP group were significantly greater than in the SAP group (P<0.01). Concentrations of hs-CRP, MCP-1, RANTES, and fractalkine in the serum of the UAP group were significantly higher than in the serum of the SAP group (P<0.05 or P<0.01), and expression of MCP-1, RANTES, and fractalkine mRNA was significantly higher than in the SAP group (P<0.05). MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.

Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism.

Our aim was to investigate the role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism. Coronary angiography and intravascular ultrasound (IVUS) were performed in 60 stable angina pectoris (SAP) patients and 60 unstable angina pectoris (UAP) patients. The chemotactic activity of monocytes in the 2 groups of patients was examined in Transwell chambers. High-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), regulated on activation in normal T-cell expressed and secreted (RANTES), and fractalkine in serum were examined with ELISA kits, and expression of MCP-1, RANTES, and fractalkine mRNA was examined with real-time PCR. In the SAP group, 92 plaques were detected with IVUS. In the UAP group, 96 plaques were detected with IVUS. The plaques in the UAP group were mainly lipid 51.04% (49/96) and the plaques in the SAP group were mainly fibrous 52.17% (48/92). Compared with the SAP group, the plaque burden and vascular remodeling index in the UAP group were significantly greater than in the SAP group (P<0.01). Chemotactic activity and the number of mobile monocytes in the UAP group were significantly greater than in the SAP group (P<0.01). Concentrations of hs-CRP, MCP-1, RANTES, and fractalkine in the serum of the UAP group were significantly higher than in the serum of the SAP group (P<0.05 or P<0.01), and expression of MCP-1, RANTES, and fractalkine mRNA was significantly higher than in the SAP group (P<0.05). MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.

Case report. Metastatic renal cell carcinoma to the left maxillary sinus.

Metastatic tumors in the paranasal sinuses are very rare. The origin of metastatic tumors in the paranasal sinuses is often renal cancer. Renal cell carcinomas are known for their tendency for early metastasis, and symptoms due to the metastatic lesion may be the only initial manifestation. In this paper, we deal with the case of a 35-year-old male patient who presented with a mass in the left maxillary region. The presence of a primary renal cell carcinoma was recognized only after surgical removal of the metastatic tumor. The presentation, diagnosis and treatment of this tumor are discussed with a review of the literature.

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)-based scaffolds for tissue engineering.

Development and selection of an ideal scaffold is of importance for tissue engineering. Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a biocompatible bioresorbable copolymer that belongs to the polyhydroxyalkanoate family. Because of its good biocompatibility, PHBHHx has been widely used as a cell scaffold for tissue engineering. This review focuses on the utilization of PHBHHx-based scaffolds in tissue engineering. Advances in the preparation, modification, and application of PHBHHx scaffolds are discussed.

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)-based scaffolds for tissue engineering

Development and selection of an ideal scaffold is of importance for tissue engineering. Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a biocompatible bioresorbable copolymer that belongs to the polyhydroxyalkanoate family. Because of its good biocompatibility, PHBHHx has been widely used as a cell scaffold for tissue engineering. This review focuses on the utilization of PHBHHx-based scaffolds in tissue engineering. Advances in the preparation, modification, and application of PHBHHx scaffolds are discussed.

Embolus-carried vascular endothelial cell growth factor 165 improves angiogenesis in thromboangiitis obliterans.

We investigated neovasculization effects of embolus-carried human vascular endothelial cell growth factor 165 (VEGF165)-encoded adenovirus (Ad) vector in the hindlimbs of rats with thromboangiitis obliterans (TAO). Rats were equally divided into blank control (I), TAO model (II), embolus (III), Ad-VEGF165 intravascular treatment (IV), Ad-VEGF165 intramuscular treatment (V), and embolus-carried Ad-VEGF165 (VI) groups. After interventional treatment, the neovasculization effect of the test gene was observed using immunohistochemistry. At 1 week after administration, compared with group II, groups V and VI had significantly increased microvessel densities, but no significant difference was observed between groups V and VI. At 2 weeks, groups V and VI exhibited significantly increased microvessel densities. At 1 week after administration, compared with group II, both groups V and VI showed a significant difference in the ratio between the α-smooth muscle actin count and the muscle fiber count, whereas no significant difference was observed between them. At 2 weeks, groups V and VI also exhibited significant differences in these ratios compared with the other groups. We conclude that Ad-VEGF165 promotes neovasculization in ischemic limbs. Embolus-carried Ad- VEGF165 had the most pronounced effect.

Microdeletion on 17p11.2 in a Smith-Magenis syndrome patient with mental retardation and congenital heart defect: first report from China.

Smith-Magenis syndrome (SMS) is a rare syndrome with multiple congenital malformations, including development and mental retardation, behavioral problems and a distinct facial appearance. SMS is caused by haploinsufficiency of RAI1 (deletion or mutation of RAI1). We describe an eight-year-old female Chinese patient with multiple malformations, congenital heart defect, mental retardation, and behavioral problems (self hugging, sleeping disturbance). High-resolution genome wide single nucleotide polymorphism array revealed a 3.7-Mb deletion in chromosome region 17p11.2. This chromosome region contains RAI1, a critical gene involved in SMS. To the best of our knowledge, this is the first report of an SMS patient in mainland China.

Neuroprotective effects of NEP1-40 and fasudil on Nogo-A expression in neonatal rats with hypoxic-ischemic brain damage.

The hypoxic-ischemic encephalopathy caused by peripartum asphyxia is a serious disease in newborn infants, and effective therapies need to be developed to reduce injury-related disorders. We evaluated the effects of NEP1-40 and fasudil on Nogo-A expression in neonatal hypoxic-ischemic brain damage (HIBD) rats. Seven-day-old Wistar rats were randomly divided into control, HIBD, NEP1-40, and fasudil groups. NEP1-40 and fasudil groups were injected intraperitoneally with these compounds. Rat brains at 6, 24, 72 h, and 7 days after HIBD were collected to determine histopathological damage and the expression levels of Nogo-A. Histopathological damage was reduced in NEP1-40 and fasudil groups compared with the untreated HIBD group. The expression of Nogo-A in the HIBD group was significantly higher than that in control, NEP1-40 and fasudil groups at the same times. Compared with the fasudil group, the expression levels of Nogo-A were significantly reduced in the NEP1-40 group. We conclude that NPE1-40 and fasudil have potential for neuroprotective effects in the neonatal rat HIBD model, mediated by inhibiting Nogo-A/ Rho pathways.

Infection characteristics of an Ecuadorian Trypanosoma cruzi strain with reduced virulence.

A human isolate of Trypanosoma cruzi obtained from Guayaquil, Ecuador (Guayas strain) was examined for its infectivity of the resistant C57Bl/6 (B6) and the susceptible C3H (He) mouse strains and compared to infection with the known virulent Brazil strain. C3H mice were capable of surviving acute Guayas infection, whereas the Brazil infection was fatal for this mouse strain. Both C3H and B6 mice showed a greatly reduced (over 10-fold) parasitemia during Guayas infection compared to Brazil infection. Histologic examination of heart tissue from Guayas-infected B6 and C3H mice indicates little inflammation, unlike what is typically seen in B6 mice chronically infected with the Brazil strain. There appears to be no remarkable difference in the anti-parasite antibody responses (as measured by ELISA and western blot) in mice infected 100 days with Guayas or Brazil parasites. Western blot analysis of the anti-heart response indicates no response during Guayas infection to a 43-kDa heart tissue glycoprotein that is a target of antibodies from B6 mice infected with Brazil strain. The Guayas strain, therefore, provides an infection that generates a low parasitemia and strong anti-parasite responses in the absence of specific anti-heart autoimmunity and obvious myocarditis. In vitro infection characteristics of these 2 parasite strains were studied in cultures of macrophages, myocytes, and fibroblasts by microscopic examination of stained slide cultures. In both short-term (24 hr) and long-term (15 day) experiments, Brazil strain infection was shown to have a greater infection rate with a higher number of parasites per cell than Guayas infection for all host cell types.(ABSTRACT TRUNCATED AT 250 WORDS)