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Background Drug-eluting balloons (DEB) have significant value for treating coronary artery disease (CAD). However, the merits of using DEB versus drug-eluting stents (DES) to treat CAD remain controversial. Herein, we conducted a meta-analysis to compare the safety and efficacy of DEB and DES for treatment of CAD. Methods We searched MEDLINE, EMBASE, and CENTRAL databases for eligible trials comparing DEB with DES for treatment of CAD. The primary endpoint was major adverse cardiac events (MACE); the secondary endpoints included in-lesion late lumen loss (LLL), binary restenosis (BR), myocardial infarction (MI), target lesion revascularization (TLR) and mortality. Results Twenty-three trials with a total of 2712 patients were included. There were no significant differences in the primary endpoint of MACE between the DEB and DES groups (Risk Ratio (RR) 1.19; 95% confidence interval (CI) (0.87, 1.63); P = 0.27), or in the clinical outcomes of each of MACE’s components, including TLR, MI and mortality. However, efficacy was significantly different between the DEB and DES groups, especially when we compared DEB to second-generation DES: in-lesion LLL (Mean Difference (MD) 0.11; (0.01, 0.22); P = 0.03); binary restenosis (RR 1.46; (1.00, 2.13); P = 0.05). Conclusions DEB is equivalent to DES in terms of safety for managing CAD, and DEB may be considered as an alternative choice for treatment of CAD. Electronic supplementary material The online version of this article (10.1186/s12872-018-0771-y) contains supplementary material, which is available to authorized users.

Background: Because of limited stability and sensitivity, circulating miRNAs as noninvasive biomarkers have not so far been used for early diagnosis and prognosis of non–small cell lung cancer (NSCLC) in clinic. Therefore, it is imperative to find more reliable biomarker(s). Methods: We performed one of most sensitive qRT-PCR assays, S-Poly(T) Plus, to select differently expressed miRNAs from genome-wide miRNA profiling. miRNA candidates were validated through a three-phase selection and two validation processes with 437 NSCLC cases and 415 controls. Results: A unique set of 7 and 9 miRNAs differed significantly in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) samples compared with those in controls, of which, there were 5 universal biomarkers for NSCLC (ADC or SCC). Ten of 11 miRNAs could discriminate early stage (stage I) of NSCLC from healthy individuals. Risk score was obtained from the validation set-1 and was tested using the ROC curves with a high area under ROC curve of 0.89 in ADC and 0.96 in SCC. Ultimately, potential biomarkers and the risk score were verified by the validation set-2 with a sensitivity of 94% and a specificity of 91.6% in ADC, and a sensitivity of 98.5% and a specificity of 51.5% in SCC, respectively. Conclusions: Taken together, 7 miRNAs and 9 miRNAs may provide noninvasive biomarkers for diagnosis and prognosis in ADC and SCC, respectively. Impact: On the basis of our sensitive and accurate method, we hope that these candidate miRNAs may have strong impact on the early lung cancer diagnosis.

Background: The use of video-assisted thoracic surgery (VATS) in the treatment of thymoma is becoming more and more common. The aim of this study was to evaluate safety and effectiveness of thoracoscopic treatment of thymoma and, more importantly, to report long-term follow-up results of a large single-center cohort. Methods: A retrospective review of a prospective database was performed. In total, 150 patients who underwent VATS resection for thymoma at Peking University People’s Hospital from April 2001 to November 2014 were retrospectively reviewed. Results: Average operation time was 140.1±54.2 min, median blood loss was 50 mL (range, 10–700 mL), median post-operative drainage time was 3 days (range, 1–11 days), and median length of post-op stay was 5 days (range, 2–20 days); 134 patients (89.3%) were followed up successfully. Median follow-up was 59.5 months (range, 2–187 months). Five- and 10-year recurrence free survival (RFS) rates of entire group were 96.5% and 94.4%, respectively; 5- and 10-year RFS rates for Masaoka stages I + II were 98.1% and 98.1%, respectively; 5- and 6-year RFS rates for Masaoka stage III were 90% and 60%, respectively. One case of recurrence in ve Masaoka stage IV patients was observed, and 4-year RFS was 80%. Multivariable analysis indicated that recurrence tended to occur in Masaoka stages III + IV patients (P=0.037, HR =12.69, 95% CI: 1.17–138.22) and older patients had a lower risk of recurrence (P=0.029, HR =0.87, 95% CI: 0.77–0.99). Myasthenia gravis (MG) presented in 44 patients (29.3%), of which 36 patients (81.8%) were followed up. Nine patients achieved complete remission, and 19 patients had symptom improvement after surgery. Overall response rate of MG was 77.8% (28/36). Conclusions: VATS was a safe and effective procedure for treatment of thymomas with satisfactory prognosis. MG with thymoma treated by VATS had comparable neurological outcome to that associated with the trans-sternal approach.

Folate (vitamin B9) is an essential nutrient required for cell survival, proliferation, differentiation and therefore embryogenesis. Folate deficiency has been associated with many diseases, including congenital heart diseases and megaloblastic anemia, yet the mechanisms underlying these remains elusive. Here, we examine the impact of folate deficiency on the development of the circulation system using a zebrafish transgenic line which displays inducible folate deficiency. Impaired hematopoiesis includes decreased hemoglobin levels, decreased erythrocyte number, increased erythrocyte size and aberrant c-myb expression pattern were observed in folate deficient embryos. Cardiac defects, including smaller chamber size, aberrant cardiac function and cmlc2 expression pattern, were also apparent in folate deficient embryos. Characterization of intracellular folate content in folate deficiency revealed a differential fluctuation among the different folate derivatives that carry a single carbon group at different oxidation levels. Rescue attempts by folic acid and nucleotides resulted in differential responses among affected tissues, suggesting that different pathomechanisms are involved in folate deficiency-induced anomalies in a tissue-specific manner. The results of the current study provide an explanation for the inconsistent outcome observed clinically in patients suffering from folate deficiency and/or receiving folate supplementation. This study also supports the use of this model for further research on the defective cardiogenesis and hematopoiesis caused by folate deficiency.

Folate is a nutrient essential for the development, function and regeneration of nervous systems. Folate deficiency has been linked to many neurological disorders including neural tube defects in fetus and Alzheimer's diseases in the elderly. However, the etiology underlying these folate deficiency-associated diseases is not completely understood. In this study, zebrafish transgenic lines with timing and duration-controllable folate deficiency were developed by ectopically overexpressing a recombinant EGFP-γ-glutamyl hydrolase (γGH). Impeded neural crest cell migration was observed in the transgenic embryos when folate deficiency was induced in early stages, leading to defective neural tube closure and hematopoiesis. Adding reduced folate or N-acetylcysteine reversed the phenotypic anomalies, supporting the causal link between the increased oxidative stress and the folate deficiency-induced abnormalities. When folate deficiency was induced in aged fish accumulation of beta-amyloid and phosphorylated Tau protein were found in the fish brain cryo-sections. Increased autophagy and accumulation of acidic autolysosome were apparent in folate deficient neuroblastoma cells, which were reversed by reduced folate or N-acetylcysteine supplementation. Decreased expression of cathepsin B, a lysosomal protease, was also observed in cells and tissue with folate deficiency. We concluded that folate deficiency-induced oxidative stress contributed to the folate deficiency-associated neuropathogenesis in both early and late stages of life.

Aims The nuclear hormone receptor estrogen-related receptor α (ERRα) regulates the activation of mitochondrial genes in various human tissues, but its role in the adrenal gland and its disorders has not been defined. Therefore, we examined ERRα expression in both normal adrenal cortex (NAC) and adrenocortical tumor (ACT) in order to study the possible correlation of ERRα with adrenal development and tumor development. Methods Human adrenal specimens (non-pathological fetal n = 7; non-pathological post-birth n = 40; aldosterone producing adenoma (APA) n = 11; cortisol producing adenoma (CPA) n = 11; adrenocortical carcinoma (ACC) n = 8) were immunohistochemically examined in this study. NAC (n = 13) and ACT (n = 28) frozen tissue specimens were also available for studying ERRα mRNA levels. Key findings In fetal NAC tissues, ERRα labeling index (LI) in fetal zone (FZ) was significantly higher that that in neocortex (NC), and the differences among age groups for overall mean LI was statistically significant when analyzed according to individual cortical layers. ERRα LI was also significantly higher in ACC than in other types of ACT. ERRα mRNA was detected in NAC and all types of ACT. Significance Results of our present study suggest a possible role of ERRα in adrenal development and ACC.

Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor for the antidiabetic agent thiazolidinedione, which exerts various physiological activities, independent of lowering blood glucose. However, the role of PPARγ in aldosterone production has not been clarified. The objective of this study was to investigate the effect of PPARγ on aldosterone synthase gene (CYP11B2) expression and aldosterone production. Localization of PPARγ expression in normal adrenal cortex was determined by immunohistochemistry. Aldosterone production and CYP11B2 expression levels were determined using human adrenocortical carcinoma H295R cells. Pioglitazone suppressed angiotensin II-induced aldosterone secretion and CYP11B2 expression. PPARγ was expressed in zona glomerulosa in human normal adrenal gland. PPARγ overexpression enhanced pioglitazone-mediated CYP11B2 transrepression. The pioglitazone-mediated suppression of aldosterone secretion and CYP11B2 expression were canceled by PPARγ L466A/E469A mutant. Pioglitazone also suppressed potassium-mediated CYP11B2 induction, but not N6-2'-O-dibutyladenosine-3',5'-cyclic monophosphate stimulation. Rosiglitazone and GW1929 also suppressed CYP11B2 transactivation. Mutation analysis revealed that the Ad1/CRE element in CYP11B2 5'-flanking region was responsible for the pioglitazone-mediated transrepression. Pioglitazone suppressed ionomycin and a truncated constitutively active form Ca(2+)/calmodulin-dependent kinase I (CaMKI)-mediated CYP11B2 transcriptional activation. A CaMK inhibitor KN-93 attenuated pioglitazone-mediated CYP11B2 transrepression. PPARγ suppresses CYP11B2 expression and aldosterone secretion.

Objective: To evaluate the clinical effects of thoracoscopy-assisted mini-open surgery for anterior column reconstruction in thoracic spinal tuberculosis. Methods: Fifty-eight patients, 35 men and 23 women, aged 39.2 (range, 19–60) years with thoracic spinal tuberculosis with an average kyphotic angle of 29.2° (range, 18°–42°) underwent thoracoscopy-assisted mini-open surgeries, including thorough debridement and anterior spinal reconstruction. According to the Frankel Grading system, preoperative neurological function was judged as Grade B in 3 cases, Grade C in 7, Grade D in 28, and Grade E in 20. All patients were followed up for an average of 4.6 years. Outcomes were evaluated retrospectively. Results: Surgery was accomplished successfully in all cases. The average operation time was 230 min (range, 180–320 min), the average intraoperative blood loss 570 ml (range, 350–1200 ml), and the mean drainage duration 3.6 days (3–5 days). Complications occurred in 19 patients (32.8%). Neurological improvement of one to three grades had occurred in 29 patients by final follow-up. The average correction rate of the kyphotic angle was 36.4%, and no obvious correction loss was detected during follow-up. No recurrent tuberculosis was found in the group. Conclusions: Thoracoscopy-assisted mini-open surgery provides a simple, safe, effective, and practical technology with minimal invasiveness for the treatment of thoracic spinal tuberculosis.

Age-related morphologic development of human adrenal zona reticularis (ZR) has not been well examined. Therefore, in this study, 44 human young adrenal autopsy specimens retrieved from large archival files (n=252) were examined for immunohistochemical and morphometric analyses. Results demonstrated that ZR became discernible around 4 years of age, and both thickness and ratio per total cortex of ZR increased in an age-dependent fashion thereafter, although there was no significant increment in total thickness of developing adrenal cortex. We further evaluated immunoreactivity of both KI67 and BCL2 in order to clarify the equilibrium between cell proliferation and apoptosis in the homeostasis of developing human adrenals. Results demonstrated that proliferative adrenocortical cells were predominantly detected in the zona glomerulosa and partly in outer zona fasciculata (ZF) before 4 years of age and in ZR after 4 years of age, but the number of these cells markedly decreased around 20 years of age. The number of BCL2-positive cells increased in ZR and decreased in ZF during development. Adrenal androgen synthesizing type 5 17β-hydroxysteroid dehydrogenase (HSD17B5 or AKR1C3 as listed in the Hugo Database) was almost confined to ZR of human adrenals throughout development. HSD17B5 immunoreactivity in ZR became discernible and increased from around 9 years of age. Results of our present study support the theory of age-dependent adrenocortical cell migration and also indicated that ZR development is not only associated with adrenarche, but may play important roles in an initiation of puberty.

Androstenedione is a common precursor of sex steroids produced and secreted in the human adrenal gland and produced by 3β-hydroxysteroid dehydrogenase (3βHSD), 17α-hydroxylase/17-20 lyase (CYP17) and cytochrome b5 (CYB5A). 3βHSD is expressed in the zona glomerulosa (ZG) and fasciculata (ZF), CYP17 in the ZF and zona reticularis (ZR) and CYB5A in the ZR, respectively. We previously demonstrated the presence of cortical parenchymal cells co-expressing 3βHSD and CYB5A with hybrid features of both ZF and ZR in human adrenal cortex and hypothesized that these cells may play an important role in androstenedione production in human adrenal gland. Age-related morphologic development of these hybrid cells has, however, not been studied. Therefore, in this study, 48 human adrenal specimens from various age groups were retrieved. Double-immunohistochemical analyses were used in order to study the correlation between this hybrid cell type and age. In both male and female adrenal cortex, the mean of total adrenocortical area, the area of CYB5A positive cells and the mean of its ratio reached highest peak in the 21–40 year-old (y.o.). The greatest overlap between 3βHSD and CYB5A in both total and relative area was present in the 13–20 y.o. group. For all of the markers above, statistically significant differences were detected among the different age groups examined (P

Androstenedione is one of several weak androgens produced in the human adrenal gland. 3β-Hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) are both required for androstenedione production. However, previous studies demonstrated the expression of HSD3B2 within the zona glomerulosa (ZG) and fasciculata (ZF) but low levels in the zona reticularis. In contrast, CYB5A expression increases in the zona reticularis (ZR) in human adrenal glands. Although their colocalization has been reported in gonadal theca and Leydig cells this has not been studied in the human adrenal. Therefore, we immonolocalized HSD3B2 and CYB5A in normal human adrenal glands and first demonstrated their co-expression in the cortical cells located at the border between the ZF and ZR in normal human adrenal. Results of in vitro studies using the human adrenal H295R cells treated with the HSD3B2 inhibitor, trilostane, also demonstrated a markedly decreased androstenedione production. Decreasing CYB5A mRNA using its corresponding siRNA also resulted in significant inhibition of androstenedione production in the H295R cells. These findings together indicate that there are a group of cells co-expressing HSD3B2 and CYB5A with hybrid features of both ZF and ZR in human adrenal cortex, and these hybrid cortical cells may play an important role in androstenedione production in human adrenal gland.

We used zebrafish as a model to study the biological functions of NF-YB during early development. Both RT-PCR and whole-mount in situ hybridization experiments revealed that nf-yb was a maternally inherited gene. Later, its expression was restricted in the future head cartilages as well as in the developing notochord. Embryos after injection with nf-yb -morpholino displayed reduced-head phenotypes, including smaller head (WT, length of head, L: 0.515 ± 0.019 mm, width of head, W: 0.323 ± 0.077 mm; nf-yb -morphant, L: 0.347 ± 0.037 mm; W: 0.266 ± 0.018 mm), sharpen Meckel's cartilage, loss of ceratobranchial, and enlarged angles of ceratohyal (WT: 72.6 ± 9.4°; nf-yb -morphant: 110.0 ± 32.5°). Subsequently, those abnormalities can be rescued after injection with capped nf-yb mRNA. TUNEL assay suggested that large amounts of cell apoptosis appeared in the head region of nf-yb -morphants. Staining with digoxigenin-labeled dlx 2a, sox 9a, runx2b and col 2a1 riboprobes showed that nf-yb -morphants displayed reduced amounts of cranial neural crest cells which are required for mandibular and branchial arches formation. These observations clearly indicate that knockdown of nf-yb translation induced parts of cranial neural crest cells apoptosis, affected cartilages formation and consequently caused reduced-head phenotypes. These findings uncover a novel and unexpected role for NF-YB as a critical modulator of neural crest cell's gene expression governing embryonic cartilage growth.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract. Less than 1% occurs in the esophagus. Surgery is the primary treatment for patients with GISTs. We report a 29-year-old male was admitted after the detection of a posterior mediastinal mass during work-up with routine examination. He did not have any disease-related symptoms. The physical examination was unremarkable. Chest computed tomographic scan, the barium esophagogram and endoscopic esophageal ultrasound showed benign neoplasm. The patient was performed an enucleation surgery through the right posterolateral thoracotomy. The pathology revealed a 13.0 cm × 12.0 cm × 5.0 cm mass. The tumor was CD117 (C-kit), PDGFRA and DOG1 positive. These findings were consistent with a GIST of the esophagus. So the diagnosis of GIST of esophagus was confirmed. The pathological diagnosis of low grade of GIST of esophagus was confirmed. The patient has no evidence of recurrence and is in good clinical conditions up-to date, five years after surgery.