Search

Esophageal cancer is one of the most lethal cancers worldwide with poor survival and limited therapeutic options. The discovery of microRNAs created a new milestone in cancer research. miR-377 is located in chromosome region 14q32, which is frequently deleted in esophageal squamous cell carcinoma (ESCC), but the biological functions, clinical significance and therapeutic implication of miR-377 in ESCC are largely unknown. In this study, we found that miR-377 expression was significantly downregulated in tumor tissue and serum of patients with ESCC. Both tumor tissue and serum miR-377 expression levels were positively correlated with patient survival. Higher serum miR-377 expression was inversely associated with pathologic tumor stage, distant metastasis, residual tumor status and chemoradiotherapy resistance. The roles of miR-377 in suppressing tumor initiation and progression, and the underlying molecular mechanisms were investigated. Results of in vitro and in vivo experiments showed that miR-377 overexpression inhibited the initiation, growth and angiogenesis of ESCC tumors as well as metastatic colonization of ESCC cells, whereas silencing of miR-377 had opposite effects. Mechanistically, miR-377 regulated CD133 and VEGF by directly binding to their 3′ untranslated region. Moreover, systemic delivery of formulated miR-377 mimic not only suppressed tumor growth in nude mice but also blocked tumor angiogenesis and metastasis of ESCC cells to the lungs without overt toxicity to mice. Collectively, our study established that miR-377 plays a functional and significant role in suppressing tumor initiation and progression, and may represent a promising non-invasive diagnostic and prognostic biomarker and therapeutic strategy for patients with ESCC.

ObjectivesIndividual neuroimaging features of small vessel disease (SVD) have been reported to influence poststroke cognition. This study aimed to investigate the joint contribution and strategic distribution patterns of multiple types of SVD imaging features in poststroke cognitive impairment.MethodsWe studied 145 first-ever ischaemic stroke patients with MRI and Montreal Cognitive Assessment (MoCA) examined at baseline. The local burdens of acute ischaemic lesion (AIL), white matter hyperintensity, lacune, enlarged perivascular space and cross-sectional atrophy were quantified and entered into support vector regression (SVR) models to associate with the global and domain scores of MoCA. The SVR models were optimised with feature selection through 10-fold cross-validations. The contribution of SVD features to MoCA scores was measured by the prediction accuracy in the corresponding SVR model after optimisation.ResultsThe combination of the neuroimaging features of SVD contributed much more to the MoCA deficits on top of AILs compared with individual SVD features, and the cognitive impact of different individual SVD features was generally similar. As identified by the optimal SVR models, the important SVD-affected regions were mainly located in the basal ganglia and white matter around it, although the specific regions varied for MoCA and its domains.ConclusionsMultiple types of SVD neuroimaging features jointly had a significant impact on global and domain cognitive functionings after stroke on top of AILs. The map of strategic cognitive-relevant regions of SVD features may help clinicians to understand their complementary impact on poststroke cognition.

Post-transplantation primary central nervous system lymphoma is an uncommon and fatal post-transplant lymphoproliferative disorder. Such lymphomas have been described in only a few case series in the literature. The incidence of this condition is rising with improved survival after organ transplantation. A case of post-transplantation primary central nervous system lymphoma in a young Chinese woman with systemic lupus erythematosus is described here. She presented with right-sided weakness and memory loss after tooth extraction 2 weeks before admission. Contrast computed tomography of the brain demonstrated a contrast rim-enhancing lesion over the left frontal lobe. With a history of recent dental procedure, long-term immunosuppressive therapy and computed tomography findings, cerebral abscess was highly suspected. Emergency operation was performed. Histopathology showed post-transplantation primary central nervous system lymphoma, with cells positive for B-cell marker CD20. Immunosuppressant was stopped and she was treated with radiotherapy and rituximab (anti-CD20 monoclonal antibody). She remained disease-free at 16 months. Post-transplantation primary central nervous system lymphoma is rare with variable presentation and radiological features. We believe rituximab may have a role in the treatment of such lymphomas.

It remains unanswered whether persistent allergic inflammation in nasal mucosa alters bacterial colonization and infection. The aim of this study was to investigate the bacterial flora in the nasal cavity of patients with persistent allergic rhinitis (PAR) and to correlate the bacteriological findings with presence of nasal symptoms, nasal eosinophil and neutrophil counts. A total of 255 subjects, aged between 6 - 74 years (mean 33.9 years) was randomly selected from a population-based rhinitis survey study in Singapore. All subjects went through a thorough medical history and nasal examinations. Serum specific IgE to a panel of common house dust mites, nasal cytological and microbiological examinations were performed. PAR was diagnosed in 107 patients and none of them had received previous regular therapy. There is a significant relationship between PAR and eosinophil grades, but not with neutrophil count. No statistically significant difference was found in quantitative and qualitative bacterial flora in nasal cavity between PAR patients and subjects with non-rhinitis or with non-allergic rhinitis. There is a significant inverse correlation between ongoing rhinorrhoea and quantitative bacterial load, and between signs of nasal mucosa (pale and edema) and the presence and type of bacterial pathogens. In conclusion, our study demonstrates that patients with untreated (or using PRN medicine) PAR do not result in a significant change in bacterial flora in their nasal cavity.

1. A recombinant adenovirus encoding SARS coronavirus(SARS-CoV) nucleocapsid protein (rAd-N) was constructed. 2. The ability of the rAd-N to induce anti-SARS-CoV N antibody production and cellular immune responses was evaluated in an HLA-A2.1/Kb transgenic mouse model.

Treatment of long, diffuse in-stent restenosis remains a therapeutic challenge. We report the successful use of multiple sirolimus-eluting stents (three 33-mm long stents) in a long, diffuse in-stent restenotic lesion. No major adverse cardiovascular events, including acute/subacute/delayed stent thrombosis, were noted at ten months. Angiography at six months showed widely patent stents with 19% restenosis only at the worst segment.

We report our early experience in using the PercuSurge GuardWire Plus system as a distal protection device in patients with acute coronary syndrome and acute myocardial infarction. Forty-three patients received percutaneous coronary intervention with the GuardWire Plus system. Thirteen had unstable angina, five had non-Q myocardial infarction and 25 had ST segment elevation myocardial infarction. Forty-one target lesions were in native coronary vessels and two were in saphenous vein grafts. Total occlusion occurred in 18 patients. The mean occlusion time by the distal protective balloon was 262.8±114.1 s. Preoperatively, TIMI 0 flow was present in 18, TIMI II flow in two and TIMI III flow in 23 patients. Post-operatively, TIMI II and TIMI III flow were established in two and 41 patients, respectively. All procedures were successful and the GuardWire Plus system was successfully deployed in all but two patients. There was no procedure-related major adverse clinical event. There was no major adverse clinical event at 30 days. There was no device-related complication. We believe that the GuardWire Plus system is safe and feasible in patients with acute coronary syndrome and acute myocardial infarction.

Sclerosing peritonitis (SP) is an uncommon but serious complication of CAPD with various suggested etiologies. We have documented 14 cases of SP in 18 patients who had used chlorhexidine in alcohol (ChA) in the connection procedure for CAPD. Thirteen died. Nine of the 14 patients had been transferred to hemodialysis or renal transplantation, yet all still developed symptoms of SP within a few months after transfer - even the 5 who were originally asymptomatic. The main symptoms of SP were peritoneal ultrafiltration failure, exudative bloody ascites and intestinal obstruction. They presented at around 5 years (30-80 months) after commencement of CAPD. Most deaths were related to intestinal obstruction. Four other patients with a comparable duration of ChA exposure were continued on CAPD with the Travenol Spike System (TSS), without further exposure to ChA. They were all asymptomatic of SP after 9-12 months. Comparing the 2 groups of asymptomatic patients, those transferred to TSS had a much better outcome after 9 months than those transferred to HD or renal transplantation (P = 0.0476). We suggest that ChA is the main cause of SP in our patients and that continuing CAPD without further exposure to ChA is a better alternative than stopping CAPD to prevent the progression of SP.

The study was performed in the area of distribution of tropical malaria resistant to 4-aminoquinolines (Vietnam) on 30 patients receiving lariam (mefloquine). The results were compared to the standard therapy with quinine and fansidar. They indicate a high efficacy of and a good tolerance to the drug tested. The use of lariam leads to a more rapid (as compared to the standard treatment) elimination of parasitemia and complete eradication of the disease relapses. The findings make it possible to recommend lariam for the prevention and treatment of tropical malaria.

Sclerosing peritonitis (SP) is an uncommon but serious complication of CAPD with various suggested etiology. We have documented 14 cases of SP in 18 CAPD patients using chlorhexidine in alcohol (ChA) in the connection procedure; 13 died. Nine of the 14 patients had been transferred to haemodialysis or renal transplantation, yet all still developed symptoms of SP within a few months after transfer even though 5 of them were originally asymptomatic. The main symptoms of SP were peritoneal ultrafiltration failure, exudative bloody ascites and intestinal obstruction. They present at around 5 years (30-80 months) after commencement of CAPD. Four other patients with a comparable duration of ChA exposure were continued on CAPD with a Travenol Spike System (TSS) without further exposure to ChA. They were all asymptomatic of SP after 9-12 months. Comparing the 2 groups of asymptomatic patients at 9 months after transfer, those transferred to TSS have a much better outcome than those transferred to HD or renal transplantation (P = 0.0476). We concluded that ChA is the main cause of SP in our patients and continuing CAPD without further exposure to ChA is a better alternative than stopping CAPD in preventing the progression of SP.

The present studies were initiated to study peroxidase and its possible regulation by estrogen in normal mammary glands. The activity of peroxidase was measured biochemically using guaiacol as the substrate for oxidation. Significant levels of peroxidase activity were associated with the particulate fraction of mammary glands from virgin mice, pregnant mice, and mice undergoing lactational involution. However, during lactation there was no detectable level of peroxidase activity in the mammary glands. Although ovariectomy led to a decrease in mammary peroxidase, detailed studies using various hormonal manipulations revealed that mammary peroxidase was perhaps not a product of estrogen action alone, but might be the result of a complex hormonal control related to growth. Alternatively, a critical evaluation of all of the data obtained with mammary glands and a comparison of these data obtained with the uterus also suggest that the presence of peroxidase in mammary glands may be due to infiltration of eosinophils and macrophages in these tissues resulting from mast cell degranulation.

In acute experiments on anesthetized cats with artificial respiration and isolated autohemoperfusion of the cerebral vessels by the pump of stabilized capacity (heparin was injected intravenously), cerebral ischemia was evoked by the stopping of the perfusion pump for 15 minutes. In the postischemic period (after perfusion resumption), 2 phases of the perfusion pressure (PP) changes were noted: at the beginning the PP lowering followed by the long-term increase (above the basic level). It is assumed that the PP changes reflect the time course of the development of suggestive postischemic cerebrovascular phenomena: hyper- and hypoperfusion. Preliminary intravenous injection (40-90 min before ischemia) of strophanthine and celanide (0.05 and 0.1 mg/kg) enhanced and extended the first phase and hampered the development of the second phase PP changes. Administration of strophanthine 90-120 min after ischemia (during the PP increase phase) did not alter the cerebrovascular resistance to the blood flow. Under these conditions the response of the cerebral vessels to strophanthine decreased as compared to that in intact (non-ischemized) cats.

It has been demonstrated in acute experiments on anesthetized cats that the control group animals manifested (before glycoside administration) a comparatively steady brain circulation accompanied by changes in the arterial pressure (AP) within 60-150 mm Hg. Intravenous injection of strophanthine (0.05 mg/kg) and celanide (0.1 mg/kg) improved autoregulatory reaction of the brain vessels during AP falling to lower levels as compared to control.