MED27 promotes malignant behavior of cells by affecting Sp1 in breast cancer.

OBJECTIVE: The aim of this study was to investigate the expression of mediator complex subunit 27 (MED27) in breast cancer (BC) and explore its effects on the proliferation and apoptosis of BC cells. PATIENTS AND METHODS: The expression of MED27 in 60 BC tissues and para-cancer tissues was detected. Based on the significantly high expression level of MED27 in tumors, the tumor samples were divided into high-expression group and low-expression group according to the median standard, with 30 samples in each group. Then, the association between MED27 expression and clinicopathological features of patients was analyzed. The correlation between MED27 expression and survival time of patients was estimated using the Kaplan-Meier method. Next, the expression level of MED27 in cells was also measured using qRT-PCR assay. In vitro study, si-MED27 was designed to interfere with the expression of MED27 in MDA-MB-231 cells. To further explore the mechanism of MED27 in BC, the expression level of SP1 in cells was examined after different treatments. RESULTS: In quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, MED27 was found to be highly expressed in both BC tissues and cells. Then, the relationship between MED27 expression and clinical pathological data was statistically analyzed, and it was found that MED27 expression was correlated with tumor size and grade. In the 60-month follow-up and Kaplan-Meier analysis, patients with high expression of MED27 had a poor prognosis. In in vitro study, MED27 expression in cells was down-regulated by transfection with si-MED27. Western blot (WB) analysis suggested that si-MED27 could effectively reduce the protein expression level of MED27 in cells, and the specificity protein 1 (Sp1) expression was also limited. In CCK-8, clone formation and flow cytometry experiments, the proliferation of cells with low MED27/Sp1 expression was suppressed, while cell apoptosis was promoted. CONCLUSIONS: MED27 acted as an oncogene in BC. By affecting Sp1, MED27 could be a new therapeutic target for the treatment of BC.

Utilizing integrating network pharmacological approaches to investigate the potential mechanism of Ma Xing Shi Gan Decoction in treating COVID-19.

Beginning in December 2019, coronavirus disease 2019 (COVID-19), due to 2019-nCoV infection, emerged in Wuhan and spread rapidly throughout China and even worldwide. Employing combined therapy of modern medicine and traditional Chinese medicine has been proposed, in which Ma Xing Shi Gan Decoction (MXSGD) was recommended as a basic prescription and applied widely in the clinical treatment of COVID-19. We investigated the underlying mechanism of MXSGD in treating COVID-19 utilizing the approaches of integrating network pharmacology. A total of 97 active ingredients of MXSGD were screened out, and 169 targets were predicted. The protein-protein interaction network exhibited hub targets of MXSGD, such as Heat shock protein 90, RAC-alpha serine/threonine-protein kinase, Transcription factor AP-1, Mitogen-activated protein kinase 1, Cellular tumor antigen p53, Vascular endothelial growth factor A, and Tumour necrosis factor. Gene Ontology functional enrichment analysis demonstrated that the biological processes altered within the body after taking MXSGD were closely related to the regulation of such processes as the acute inflammatory response, chemokine production, vascular permeability, response to oxygen radicals, oxidative stress-induced apoptosis, T cell differentiation involved in the immune response, immunoglobulin secretion, and extracellular matrix disassembly. KEGG enrichment analysis indicated that the targets of MXSGD were significantly enriched in inflammation-related pathways, immunomodulation-related pathways, and viral infection-related pathways. The therapeutic mechanisms of MXSGD on COVID-19 may primarily involve the following effects: reducing inflammation, suppressing cytokine storm, protecting the pulmonary alveolar-capillary barrier, alleviating pulmonary edema, regulating the immune response, and decreasing fever.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) promotes EGF receptor signaling of oral squamous cell carcinoma metastasis via the complex N-glycosylation.

Aberrant protein glycosylation could be a distinct surface-marker of cancer cells that influences cancer progression and metastasis because glycosylation can regulate membrane protein folding which alters receptor activation and changes epitope exposure for antibody (Ab) recognition. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycophosphoinositol-anchored protein, is a heavily glycosylated tumor antigen. However, the clinical significance and biological effect of CEACAM6 glycosylation has not been addressed in cancers. We recently developed an anti-CEACAM6 Ab (TMU) from an immune llama library which can be engineered to a single-domain (sd)Ab or a heavy-chain (HC)Ab. The TMU HCAb specifically recognized glycosylated CEACAM6 compared to the conventional antibodies. Using the TMU HCAb, we found that glycosylated CEACAM6 was a tumor marker associated with recurrence in early-stage OSCC (oral squamous cell carcinoma) patients. CEACAM6 promoted OSCC cell invasion, migration, cytoskeletal rearrangement, and metastasis via interaction with epidermal growth factor (EGF) receptor (EGFR) and enhancing EGFR activation, clustering and intracellular signaling cascades. These functions were modulated by N-acetylglucosaminyltransferase 5 (MGAT5) which mediated N-glycosylation at Asn256 (N256) of CEACAM6. Finally, the TMU sdAb and HCAb treatment inhibited the migration, invasion and EGF-induced signaling in CEACAM6-overexpressing cells. In conclusion, the complex N-glycosylation of CEACAM6 is critical for EGFR signaling of OSCC invasion and metastasis. Targeting glycosylated CEACAM6 with the TMU sdAb or TMU HCAb could be a feasible therapy for OSCC.

MCT-1 expression and PTEN deficiency synergistically promote neoplastic multinucleation through the Src/p190B signaling activation.

Multinucleation is associated with malignant neoplasms; however, the molecular mechanism underlying the nuclear abnormality remains unclear. Loss or mutation of PTEN promotes the development of malignant tumors. We now demonstrate that increased expression of the oncogene MCT-1 (multiple copies in T-cell malignancy 1) antagonizes PTEN gene presentation, PTEN protein stability and PTEN functional activity, thereby further promoting phosphoinositide 3 kinase/AKT signaling, survival rate and malignancies of the PTEN-deficient cells. In the PTEN-null cancer cells, MCT-1 interacts with p190B and Src in vivo, supporting that they are in proximity of the signaling complexes. MCT-1 overexpression and PTEN loss synergistically augments the Src/p190B signaling function that leads to inhibition of RhoA activity. Under such a condition, the incidence of mitotic catastrophes including spindle multipolarity and cytokinesis failure is enhanced, driving an Src/p190B/RhoA-dependent neoplastic multinucleation. Targeting MCT-1 by the short hairpin RNA markedly represses the Src/p190B function, improves nuclear structures and suppresses xenograft tumorigenicity of the PTEN-null breast cancer cells. Consistent with the oncogenic effects in vitro, clinical evidence has confirmed that MCT-1 gene stimulation is correlated with p190B gene promotion and PTEN gene suppression in human breast cancer. Accordingly, MCT-1 gene induction is recognized as a potential biomarker of breast tumor development. Abrogating MCT-1 function may be a promising stratagem for management of breast cancer involving Src hyperactivation and/or PTEN dysfunction.

Cardiac rehabilitation in a pediatric patient with heart retransplantation. A single case study.

BACKGROUND: Cardiac rehabilitation (CR) after heart transplantation is known to benefit physical capacity in adults, but the advantages of CR on pediatric patients with heart retransplantation remain undetermined. AIM: The purpose of the present study was to report the effect of structured CR for a boy receiving heart transplantations twice. DESIGN: Single case study. SETTING: Inpatient and outpatient rehabilitation department. POPULATION: A pediatric patient underwent heart transplantation due to dilated cardiomyopathy at 13.6 year-old and retransplantation owing to severe cardiac allograft vasculopathy at 16.2 year-old. METHODS: CR was arranged after both transplantations. Bicycle or treadmill exercises were conducted three times weekly with the intensity adjusted to the ventilatory threshold. Serial cardiopulmonary exercise tests were performed to evaluate the sequential cardiorespiratory function changes using the peak oxygen uptake (VO2peak) as the primary outcome. RESULTS: The patient had undergone 10 times of exercise tests during rehabilitation. The VO2peak increased from 12.27 to 15.63 mL·kg-1·min-1 within 6 months after the primary transplantation. However, the VO2peak dropped intensively after a rejection episode and failed to improve since the development of cardiac allograft vasculopathy. Following retransplantation, the VO2peak appeared worse initially but increased gradually with rehabilitation. One year subsequent to retransplantation, the VO2peak reached 17.7 mL·kg-1·min-1 with a 7.22 mL·kg-1·min-1 improvement compared with his baseline value. CONCLUSION: Structured CR improves aerobic capacity of a pediatric patient with heart retransplantation. CLINICAL REHABILITATION IMPACT: CR is safe and beneficial for pediatrics with heart retransplantation. Cardiopulmonary exercise testing can be considered as an adjuvant tool for detecting rejection or cardiac allograft vasculopathy in pediatric heart transplantation recipients.

Endothelin-1 promotes vascular endothelial growth factor-dependent angiogenesis in human chondrosarcoma cells.

Chondrosarcoma is the second most common sarcoma in bone malignancy and is characterized by a high metastatic potential. Angiogenesis is essential for the cancer metastasis. Endothelin-1 (ET-1) has been implicated in tumor angiogenesis and metastasis. However, the relationship of ET-1 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma cells is mostly unknown. Here, we found that the expression of ET-1 and VEGF were correlated with tumor stage and were significantly higher than that in the normal cartilage. Exogenous ET-1 with chondrosarcoma cells promoted VEGF expression and subsequently increased migration and tube formation in endothelial progenitor cells. ET-1 increased VEGF expression and angiogenesis through ETAR, integrin-linked kinase (ILK), Akt and hypoxia-inducible factor-1α (HIF-1α) signaling cascades. Knockdown of ET-1 decreased VEGF expression and also abolished chondrosarcoma conditional medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. In addition, in the xenograft tumor angiogenesis model, knockdown of ET-1 significantly reduced tumor growth and tumor-associated angiogenesis. Taken together, these results indicate that ET-1 occurs through ETAR, ILK and Akt, which in turn activates HIF-1α, resulting in the activation of VEGF expression and contributing to the angiogenesis and tumor growth of human chondrosarcoma cells.

Radiological manifestations of pulmonary tuberculosis in patients subjected to anti-TNF-α treatment.

SETTING: The risk of pulmonary tuberculosis (PTB) may increase with increased use of anti-tumour necrosis factor (TNF) treatment in inflammatory arthritis. OBJECTIVE: To evaluate the impact of anti-TNF treatment on radiological manifestations of PTB. METHOD: Between January 2007 and December 2012, the chest radiographs (CXRs) of 23 consecutive patients with newly diagnosed PTB who underwent anti-TNF treatment were studied. Chest computed tomography (CT) images were available for 14. To compare the radiological features of PTB, the CXRs of 46 immunocompetent PTB patients with similar demographics were studied as controls, of whom 34 underwent chest CT. Two radiologists and one chest physician reviewed the chest images independently. RESULTS: Compared with the controls, fibronodular lesions were less common on CXR in the anti-TNF group (P < 0.001). In contrast, lymphadenopathy (P < 0.001), pleural effusion (P = 0.015) and pericardial effusion (P = 0.02) were more common, while tree-in-bud appearance (P = 0.017) was less commonly depicted on chest CT in the anti-TNF group. Although there was no significant difference in zonal predilection and laterality of the lesions between the two groups, diffuse lesions (P = 0.004) on chest CT scans were more frequent in the anti-TNF group. CONCLUSION: Unusual presentations of PTB were more common in the CXRs and/or CT scans of patients who underwent anti-TNF treatment.

Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells.

MicroRNAs (miRNAs) are thought to control tumor metastasis through direct interactions with target genes. Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. However, the issue of whether miRNAs participate in T3/TR-mediated tumor migration is yet to be established. In the current study, we demonstrated that T3/TR negatively regulates mature miR-17 transcript expression, both in vitro and in vivo. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays localized the regions responding to TR-mediated repression to positions -2234/-2000 of the miR-17 promoter sequence. Overexpression of miR-17 markedly inhibited cell migration and invasion in vitro and in vivo, mediated via suppression of matrix metalloproteinases (MMP)-3. Moreover, p-AKT expression was increased in miR-17-knockdown cells that led to enhanced cell invasion, which was blocked by LY294002. Notably, low miR-17 expression was evident in highly metastatic cells. The cell migration ability was increased by T3, but partially reduced upon miR-17 overexpression. Notably, TRα1 was frequently upregulated in hepatocellular carcinoma (HCC) samples and associated with low overall survival (P=0.023). miR-17 expression was significantly negatively associated with TRα1 (P=0.033) and MMP3 (P=0.043) in HCC specimens. Data from our study suggest that T3/TR, miR-17, p-AKT and MMP3 activities are interlinked in the regulation of cancer cell metastasis.

The use of hypoxic cultured mesenchymal stem cell for oncolytic virus therapy.

The safety of oncolytic viruses, such as conditionally replicative adenoviruses (CRAds), has been validated in clinical trials for cancer therapy. Their antitumor efficacy is limited by the presence of preexisting neutralizing antibodies (NAbs). Mesenchymal stem cells (MSCs) are attractive as a cellular vehicle to carry antitumor agents, not only because they are easily obtained and expanded to great numbers in vitro, but also because of their ability to migrate and engraft to tumors. MSCs expanded under hypoxic conditions decrease in replicative senescence and increase in proliferation capacity and differentiation potentials. However it remains to be clarified whether these hypoxic MSCs also are good carriers for the delivery of CRAds to tumor cells in the presence of NAbs. This study firstly demonstrated hypoxic MSCs with an increased ability to migrate toward tumors through the upregulation of chemokine receptors, such as CXCR4 and CX3CR1. It is then demonstrated that hypoxic MSCs has the capacity to carry CRAds, without inducing apoptosis, for up to one week. Using an in vitro coculture with human colon cancer cells and with intraperitoneally (i.p.) and subcutaneously (s.c.) developed human colon cancer xenografts, it is demonstrated that hypoxic MSCs are able to protect CRAds from attack by NAbs, thereby successfully delivering them to the target tumor cells. These results show that hypoxic MSCs can serve as cell carriers for CRAds and may help to develop new strategies against cancer.

Thyroid hormone suppresses cell proliferation through endoglin-mediated promotion of p21 stability.

Hypothyroidism has been associated with significantly elevated risk for hepatocellular carcinoma (HCC), although the precise underlying mechanisms remain unknown at present. Thyroid hormone (T3) and its receptor (TR) are involved in metabolism and growth. Endoglin is a T3/TR candidate target gene identified from our previous studies. Here, we demonstrated that T3 positively regulates endoglin mRNA and protein levels, both in vitro and in vivo. The thyroid hormone response elements of endoglin were identified at positions -2114/-2004 and -2032/-1973 of the promoter region using the electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Endoglin was downregulated in the subgroups of HCC patients and significantly associated with histology grade (negative association, P=0.001), and this expression level was significantly associated with TRα1 in these HCC patients. Our results clearly indicate that p21 is involved in T3-mediated suppression of cell proliferation. Knock down of endoglin expression in HCC cells facilitated p21 polyubiquitination and promoted cell proliferation in the presence of T3. The data collectively suggest that T3/TR signaling suppresses cell proliferation by upregulating endoglin, in turn, affecting p21 stability. The results indicate that endoglin has a suppressor role to inhibit cell proliferation in HCC cell lines.

Proficiency of drug susceptibility testing for Mycobacterium tuberculosis in Taiwan, 2007-2011.

SETTING: Authorised clinical mycobacteriology laboratories in Taiwan. OBJECTIVE: To evaluate the impact of external quality assessment (EQA) on the quality of drug susceptibility testing (DST) in 2007-2011. DESIGN: Panels consisting of 20-30 Mycobacterium tuberculosis strains were used. Efficiency of 95% in detecting resistance to both isoniazid (INH) and rifampicin (RMP), and of 90% to ethambutol (EMB) and streptomycin (SM) was used to define a competent laboratory. RESULTS: The proportion of laboratories that fulfilled the competency criteria for all first-line drugs was 16.7% in 2007, increasing to 85.7% in 2008, 86.1% in 2009, 82.4% in 2010, and to 96.8% in 2011 (P < 0.01). The mean efficiency in detecting resistance to INH and RMP reached >99% during 2008-2011 (P = 0.90 for INH and P = 0.82 for RMP), and for EMB it increased from 82.0% in 2007 to 92.2% in 2008 and 99.5% in 2011 (P < 0.01), while that for resistance to SM increased from 82.0% in 2007 to 98.1% in 2008 and 99.5% in 2011 (P < 0.01). Preparations of inoculum for DST and detection of EMB resistance were the main reasons for non-competence. CONCLUSION: The EQA programme was effective in improving the competency of clinical laboratories in performing DST for tuberculosis.

Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis.

BACKGROUND: The aim was to evaluate the diagnostic value of procalcitonin, C-reactive protein (CRP) and white blood cell count (WBC) in uncomplicated or complicated appendicitis by means of a systematic review and meta-analysis. METHODS: The Embase, MEDLINE and Cochrane databases were searched, along with reference lists of relevant articles, without language restriction, to September 2012. Original studies were selected that reported the performance of procalcitonin alone or in combination with CRP or WBC in diagnosing appendicitis. Test performance characteristics were summarized using hierarchical summary receiver operating characteristic (ROC) curves and bivariable random-effects models. RESULTS: Seven qualifying studies (1011 suspected cases, 636 confirmed) from seven countries were identified. Bivariable pooled sensitivity and specificity were 33 (95 per cent confidence interval (c.i.) 21 to 47) and 89 (78 to 95) per cent respectively for procalcitonin, 57 (39 to 73) and 87 (58 to 97) per cent for CRP, and 62 (47 to 74) and 75 (55 to 89) per cent for WBC. ROC curve analysis showed that CRP had the highest accuracy (area under ROC curve 0·75, 95 per cent c.i. 0·71 to 0·78), followed by WBC (0·72, 0·68 to 0·76) and procalcitonin (0·65, 0·61 to 0·69). Procalcitonin was found to be more accurate in diagnosing complicated appendicitis, with a pooled sensitivity of 62 (33 to 84) per cent and specificity of 94 (90 to 96) per cent. CONCLUSION: Procalcitonin has little value in diagnosing acute appendicitis, with lower diagnostic accuracy than CRP and WBC. However, procalcitonin has greater diagnostic value in identifying complicated appendicitis. Given the imperfect accuracy of these three variables, new markers for improving medical decision-making in patients with suspected appendicitis are highly desirable.

Isolation and identification of Acanthamoeba species related to amoebic encephalitis and nonpathogenic free-living amoeba species from the rice field.

AIMS: Isolation and characterization of the clinically relevant amphizoic amoebas in vegetated farmlands, which may present a risk to farmers' health. METHODS AND RESULTS: Acanthamoeba species was isolated and characterized via morphological and molecular means in the rice field where the patient was exposed to rice paddy water which most probably was the point of infection. An Acanthamoeba sp. abundant in the rice field was identified. Genotyping showed the strain to be genotype T4, which was identical to the amoebic parasite found in patient's cerebrospinal fluid. During the course of the study, three nonpathogenic free-living amoeba species were also isolated and characterized for the first time in Taiwan. CONCLUSIONS: This study successfully located a possible source of granulomatous amoebic encephalitis in a patient and provided the first evidence that Acanthamoeba genotype T4 may be a potential pathogen in Taiwan. SIGNIFICANCE AND IMPACT OF THE STUDY: The integration of field survey, clinical data and morphological and genetic examination represents a sound strategy for investigation of the possible role of free-living amoebae in causing human diseases. Future work should include investigating the potential contributory role of other nonpathogenic free-living protozoa in disease of livestock or even human.

Proficiency of drug susceptibility testing for Mycobacterium tuberculosis in Taiwan.

OBJECTIVE: To evaluate the impact of external quality assessment on the quality of drug susceptibility testing (DST) in clinical mycobacteriology laboratories. DESIGN: A pilot evaluation of DST proficiency was conducted in 2006 and scaled up in 2007. A panel consisting of 20 Mycobacterium tuberculosis isolates was used. Accuracy of 95% in detecting resistance to both isoniazid (INH) and rifampicin (RMP), and 90% to both ethambutol (EMB) and streptomycin (SM), was used to define a competent laboratory. RESULTS: Nine laboratories participated in 2006 and 30 in 2007. In 2006, the mean accuracy in detecting resistance to INH was 91.6%, for RMP it was 96.1%, for EMB it was 90.5% and for SM it was 93.9%. In 2007, the mean accuracy in detecting resistance to INH increased to 95.7% and that for RMP to 97.2%, while the accuracy of EMB resistance detection decreased to 82.0% and that for SM resistance to 86.8%. Quality improvement was observed in those laboratories that had adopted standardised methods. Overall, only five (17%) laboratories fulfilled the competency criteria for all four drugs in 2007. CONCLUSION: The majority of the laboratories that participated in 2006 demonstrated an improvement in DST performance in 2007. It is essential to continue external quality assessment to strengthen the quality of DST.

External quality assessment of sputum smear microscopy in Taiwan.

OBJECTIVE: To evaluate the quality of sputum smear microscopy in nine Taiwan Centers for Disease Control contract laboratories, an external quality assessment (EQA) programme has been implemented since 2005. DESIGN: A sampling strategy based on the lot quality assurance system was applied to select slides for rechecking. Supervisory visits and technical training were conducted to determine the causes of errors and to take corrective action. RESULTS: Of the 1017 slides sampled in 2005, 637 (63%) had proper smear size, 492 (48%) proper thickness and 884 (87%) proper staining; the corresponding figures were 972 (100%), 748 (77%) and 809 (99.6%) for the 972 slides rechecked in 2006. After training, the quality of size and staining of smear preparation had significantly improved (P < 0.001) in 2006. Rechecking of 981 readable slides in 2005 identified 3 (0.3%) high false-negatives, 3 (16.7%) low false-positives and 26 (2.8%) low false-negatives; the corresponding errors were 3 (0.3%), 8 (28.6%) and 12 (1.3%) for the 972 slides rechecked in 2006. Of the eight laboratories, two (25%) and four (50%) reached 80% sensitivity in 2005 and 2006, respectively. CONCLUSION: Technical training and EQA improved the quality of sputum smear microscopy services.

Circulating levels of leptin, adiposity and breast cancer risk.

The present case-control study was to investigate the relationships of plasma leptin level and anthropometric measures of adiposity with the risk of breast cancer. Questionnaire information, anthropometric measures and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei, between 2004 and 2006. Plasma levels of leptin were measured by RIA. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for assessing the associations. Overall, higher leptin concentrations were significantly associated with an increased risk of breast cancer (OR (95% CI) for top vs bottom tertile of leptin was 1.63 (1.07-2.49), P(trend)=0.009). Waist circumference was a significant anthropometric factor for breast cancer in both pre- and postmenopausal women. Furthermore, the associations of leptin with breast cancer risk remained after adjustment for obesity indices. These results suggest that leptin may have an independent role in breast tumorigenesis. Regardless of the impact of circulating leptin, more research is needed to elucidate molecular mechanisms and local leptin levels that are critical for the development of breast cancers.

An unusual cause of chylothorax after Norwood stage one reconstruction.

We report an unusual cause of prolonged chylothorax drainage after Norwood stage one reconstruction. This 1-month-old girl's chylous drainage was refractory to medical treatment. Echocardiography revealed thrombosis of the superior vena cava. Upon sternotomy to remove the thrombus, we were surprised to find the ePTFE (expanded polytetrafluoroethylene) tube previously used for selective cerebral perfusion compressing the innominate vein and the pericardium-based aortic arch. We performed a superior vena cava thrombectomy and shortened the ePTFE tube. Her chylothorax subsided gradually. We suggest that external compression of the venous drainage system should be considered in patients with prolonged chylothorax drainage. Once medical treatment fails, early surgical exploration may be helpful to stop the chylothorax.

Evolving strategies and improving outcomes of Norwood stage one reconstruction: a decade experience of a single institution in Taiwan.

AIM: The aim of this study was to define the improvement in short-term outcome and risk factors of Norwood stage one reconstruction for hypoplastic left heart syndrome (HLHS) in Taiwan, after implementing new perioperative management strategies. METHODS: Data were retrieved from a retrospective chart review of patients with HLHS treated between July 1997 and July 2007. Since we implemented new perioperative strategies in 2004, we divided our patients into two groups, early era (1997-2003) and late era (2004-2007), and compared the outcome. RESULTS: We enrolled 48 patients. In the early era group (n=28), the diagnosis was confirmed by cardiac catheterization and controlled ventilation was used to manipulate the balance between systemic and pulmonary blood flow. The survival rate was only 17.9% (5/28). Surgery was performed at 15.2+/-10.7 days, which was significantly later than in the late era group (4.6+/-4.0 days, n=20). A lower preoperative shock and more prenatal diagnoses were recorded for the late era group. RV-PA conduit was used in 17 patients in the late era group of which 12 (70.6%) survived to be discharged from hospital. The risk factor was significant TR (tricuspid regurgitation). CONCLUSIONS: With our contemporary perioperative management and change in surgical strategy, survival after first-stage palliation has improved. We believe that our HLHS experience is valuable for low volume centers and also for Asian cohorts.

Features of non-small cell lung carcinomas overlooked at digital chest radiography.

PURPOSE: To examine the imaging features of non-small cell lung carcinomas (NSCLC) overlooked at digital chest radiography (dCXR), and compare general and thoracic radiologists' performance for lung carcinoma detection at dCXR. METHODS: Frontal and lateral dCXR from 30 consecutive patients with lung carcinoma overlooked during initial interpretation and 30 normal controls were independently retrospectively reviewed by two blinded thoracic radiologists and, in a separate review, three blinded general radiologists. The location, size, histopathology, borders, presence of superimposed structures, and lesion opacity were recorded. Interobserver agreement was calculated, and the detection performance between thoracic and general radiologists was compared. RESULTS: The average patient age was 67.9 years (range 47-82 years). The average size of carcinomas missed by the thoracic radiologists was 18.1mm (range 10-32 mm). Lesion margins were circumscribed in 29% (2/7), and 71% (5/7) of missed lesions were obscured by anatomical superimposition. Seventy-one percent (5/7) of missed lesions were solid nodules on computed tomography (CT) images. Forty-three percent of lesions were located in the upper lobes and 63% were adenocarcinomas. Compared with general radiologists, the seven NSCLC missed by the thoracic radiologists tended to be smaller (p=0.063), had significantly lower CT density measurements (-92.4+/-87.5 HU versus -70+/-87.2 HU, p=0.050), and more commonly had an ill-defined margin (p=0.026). The clinical stage of the overlooked lesions did not differ between the two groups (p=0.480). CONCLUSIONS: The lesion size, location, conspicuity, and histopathology impact the likelihood of lung carcinoma detection at dCXR in a fashion similar to that of conventional film-screen techniques.

Expression of p21 and p53 in rat gingival and human oral epithelial cells after cyclosporine A treatment.

BACKGROUND AND OBJECTIVE: Expression of p21 and p53 were examined, at gene and protein levels, in edentulous gingival epithelial cells from rats and from a human oral epidermoid carcinoma cell line, OECM1, after cyclosporine A therapy. MATERIAL AND METHODS: In vivo: 20 partially edentulous SD rats were assigned into cyclosporine A feeding and control groups. After the rats were killed, p21 and p53 in gingiva were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. In vitro: after cyclosporine A treatment, p21 and p53 of OECM1 cells were evaluated by western blot and the luciferase assay. The distribution of OECM1 cells in each phase of the cell cycle was evaluated by flow cytometry. RESULTS: The mRNA expression of p21 was significantly higher in the cyclosporine A group than in the control group. A greater number of positive anti-p21-stained cells were observed in the gingival epithelium of the cyclosporine A group than in the control group. Significantly higher levels of p21 protein and activity were observed in OECM1 cells after cyclosporine A treatment than in cells without treatment. A relative increase of cells in G0/G1 phases, and a decrease of cells in G2/M phases, were observed in OECM1 cells after cyclosporine A treatment. CONCLUSION: In the present study, higher p21 mRNA and protein expressions were observed after cyclosporine A treatment. Thus, an up-regulation of p21 expression, via a p53-independent pathway, by cyclosporine A in gingival and oral epithelial cells was suggested.