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Abstract. Background:. Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established. Methods:. A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set. Results:. The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613–0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635–0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865–0.917). It had an AUC of 0.888 (95% CI: 0.842–0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509–0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544–0.675) (P

Abstract. Background. Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells. Methods. We generated Zbtb46fl/fl and Zbtb46fl/flMx1-Cre mice. The deletion of Zbtb46 in Zbtb46fl/flMx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46fl/fl and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry. Results. The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46fl/fl littermates (Zbtb46fl/flvs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46fl/flMx1-Cre mice was similar to those from Zbtb46fl/fl control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation. Conclusion. Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.

Abstract. Background:. Acute kidney injury (AKI) is a serious and fatal complication of acute myocardial infarction (AMI). It has high short- and long-term mortality rates and a poor prognosis but is potentially preventable. However, the current incidence, risk factors, and outcomes of AKI in the Chinese population are not well understood and would serve the first step to identify high-risk patients who could receive preventative care. Methods:. The medical data of 1124 hospitalized patients diagnosed with AMI from October 2013 to September 2015 were reviewed. AKI was defined according to the 2012 Kidney Disease Improving Global Outcomes criteria. All the patients were divided into either the AKI group or the non-AKI group. A univariate comparison analysis was performed to identify possible risk factors associated with AKI. A multiple logistic regression analysis was used to identify the independent risk factors for AKI in patients with AMI. Results:. Overall, the incidence of AKI was 26.0%. The mortality rate of the AKI group was 20.5%, and the mortality rate of the non-AKI group was 0.6% (P 60 years old) (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02–1.05, P = 0.000), hypertension (OR 2.51, 95% CI 1.62–3.87, P = 0.000), chronic kidney disease (OR 3.52, 95% CI 2.01–6.16, P = 0.000), Killip class ≥3 (OR 5.22, 95% CI 3.07–8.87, P = 0.000), extensive anterior myocardial infarction (OR 3.02, 95% CI 1.85–4.93, P = 0.000), use of furosemide (OR 1.02, 95% CI 1.02–1.03, P = 0.000), non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (OR 1.58, 95% CI 1.04–2.40, P = 0.032). These factors provided an accurate tool to identify patients at high risk of developing AKI. Conclusions:. Approximately 26.0% of patients undergoing AMI developed AKI, and the development of AKI was strongly correlated with in-hospital mortality. The risk factors for AKI in patients with AMI were determined to help identify high-risk patients and make appropriate clinical decisions.

Abstract. Background:. Pulmonary artery hypertension associated with congenital heart disease (PAH-CHD) occurs predominantly among patients with uncorrected CHD. Treatment of severe pediatric PAH-CHD remains a major intractability. This study evaluated the predictors and prognoses of children with PAH-CHD who underwent surgical correction. Methods:. The data for 59 children with severe PAH-CHD who underwent surgical correction, with or without postoperative medication, between May 2011 and June 2015 at the Guangdong Provincial People's Hospital were analyzed retrospectively. A regression analysis, receiver-operating characteristic (ROC) curves, and Kaplan-Meier curves were used for survival analysis. Results:. Fifty-nine children with severe PAH-CHD underwent heart catheterization and correction, with or without specific anti-PAH drugs postoperatively, were included in this study. The pulmonary pressure, heart function, and ending events were observed and median observation period was 49 ± 20 months. Twenty-eight patients (50%) received at least one additional anti-PAH drug after correction. The survival rate after 2 years was 91.5% (54/59); two patients were in a critical condition, and three were lost to follow-up. Twelve patients (29%) still received over one additional PAH-specific therapy at follow-up, whereas 42 (75%) had successfully stopped drug treatment. Two patients (3.5%) died and one underwent a second thoracotomy to remove the ventricular septal defect patch. Acute vasoreactivity test (AVT) criteria had limited efficacy in predicting pediatric PAH-CHD, whereas pulmonary vascular resistance (PVR) ≤ 6.65 Wood units (WU)/m2 or PVR/systemic vascular resistance (SVR) ≤ 0.39 during AVT indicated a good prognosis after surgical correction with an AUC of 98.3% (95% confidence interval [CI]: 96.0–100%), 98.4% (95% CI: 96.0–100%) sensitivity of 100%, 100% and specificity of 82.1%, 92.9%, respectively. Conclusions:. Although the criteria for positive AVT currently used are unsuitable for pediatric patients with PAH-CHD, PVR and PVR/SVR during AVT are excellent predictors of outcome in pediatric PAH-CHD. Surgery aided by anti-PAH drugs is an effective strategy and should be recommended for severe pediatric PAH-CHD with PVR ≤ 6.65 WU/m2 and PVR/SVR ≤ 0.39 after iloprost aerosol inhalation.

Background: The introduction of individualized abdominoperineal excision (APE) may minimize operative trauma and reduce the rate of complications. The purpose of this study was to evaluate the safety and efficacy of individualized APE for low rectal cancer. Methods: Fifty-six patients who underwent individualized APE from June 2011 to June 2015 were evaluated retrospectively in Beijing Chaoyang Hospital, Capital Medical University. The main outcome measures were circumferential resection margin (CRM) involvement, intraoperative perforation, postoperative complications, and local recurrence. Statistical analysis was performed using SPSS version 16.0. Results: Fifty (89%) patients received preoperative chemoradiotherapy: 51 (91%) patients were treated with the sacrococcyx preserved; 27 (48%) patients with the levator ani muscle partially preserved bilaterally; 20 (36%) patients with the levator ani muscle partially preserved unilaterally and the muscle on the opposite side totally preserved; 7 (13%) patients with intact levator ani muscle and part of the ischioanal fat bilaterally dissected; and 2 (4%) patients with part of the ischioanal fat and intact lavator ani muscle dissected unilaterally and the muscle on the opposite side partially preserved. The most common complications included sexual dysfunction (12%), perineal wound complications (13%), urinary retention (7%), and chronic perineal pain (5%). A positive CRM was demonstrated in 3 (5%) patients, and intraoperative perforations occurred in 2 (4%) patients. On multiple logistic regression analysis, longer operative time (P = 0.032) and more intraoperative blood loss (P = 0.006) were significantly associated with perineal procedure-related complications. The local recurrence was 4% at a median follow-up of 53 months (range: 30–74 months). Conclusion: With preoperative chemoradiotherapy, individualized APE may be a relatively safe and feasible approach for low rectal cancer with acceptable oncological outcomes.

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies. Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout. Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR)

Background: Most studies on enhanced recovery after surgery (ERAS) for gastric cancer exclude patients who received neoadjuvant chemotherapy. Here, we aimed to evaluate whether patients who received neoadjuvant chemotherapy can be enrolled into the ERAS program for locally advanced gastric cancer. Methods: From April 2015 to July 2017, 114 patients who received neoadjuvant chemotherapy for locally advanced gastric cancer were randomized into ERAS and standard care (SC) groups. Postoperative length of stay, complications, bowel function, and nutritional status were recorded. Results: The postoperative length of stay of the ERAS group was shorter compared with that of the SC group (5.9 ± 5.6 vs. 8.1 ± 5.3 days, P = 0.037). The postoperative complication rate was 9.3% in the ERAS group and 11.5% in the SC group (P = 0.700). The time to first flatus (2.7 ± 2.0 vs. 4.5 ± 4.6 days, P = 0.010) and time to a semi-liquid diet (3.2 ± 2.1 vs. 6.3 ± 4.9 days, P < 0.001) in the ERAS group were shorter compared with those in the SC group. On the 10th day after surgery, the values of weight, total protein, albumin, and prealbumin of the ERAS group were lower compared with those of the SC group. Conclusions: Patients who received neoadjuvant chemotherapy could be enrolled into ERAS programs for locally advanced gastric cancer. The nutritional status of these patients was not adversely affected.

Background: Percutaneous balloon pulmonary valvuloplasty (PBPV) is the preferred therapy for pulmonary valve stenosis (PVS). This study retrospectively reviewed recent PBPV outcomes in infants with PVS. The aim of this study was to evaluate factors associated with immediate therapeutic outcomes and restenosis during medium-term follow-up. Methods: The study included 158 infants with PVS who underwent PBPV from January 2009 to July 2015. Demographic characteristics and patient records were reviewed, including detailed hospitalization parameters, hemodynamic data before and immediately after balloon dilation, cineangiograms, and echocardiograms before PBPV and at each follow-up. All procedures were performed by more than two experienced operators. Results: Immediately after balloon dilation, the pressure gradient across the pulmonary valve decreased from 73.09 ± 21.89 mmHg (range: 43–151 mmHg) to 24.49 ± 17.00 mmHg (range: 3–92 mmHg; P < 0.001) and the right ventricular systolic pressure decreased from 95.34 ± 23.44 mmHg (range: 60–174 mmHg) to 52.07 ± 18.89 mmHg (range: 22–134 mmHg; P < 0.001). Residual transvalvular pressure gradients of 67.31 ± 15.19 mmHg (range: 50–92 mmHg) were found in 8.2% of patients, indicating poor therapeutic effects; 6.4% of patients had variable-staged restenosis at follow-up and 3.8% underwent reintervention by balloon dilation or surgical repairs. Further analysis demonstrated that the balloon/annulus ratio showed statistically significant differences (P < 0.05) among groups with different therapeutic effects and between the restenosis and no-stenosis groups. Binary logistic regression analysis further revealed that higher balloon/annulus ratio (odds ratio: 0.005, 95% confidence interval: 0–0.39) was an independent protective factor for restenosis. The rate of severe complications was 1.9%. Conclusions: PBPV is a definitive therapy for infants with PVS based on its effectiveness, feasibility, and safety. Restenosis upon medium-term follow-up is relatively rare.

Background: Transcatheter closure of congenital coronary artery fistulas (CCAFs) is an alternative therapy to surgery; however, data regarding transcatheter closure for CCAF with a giant coronary artery aneurysm (CAA) in pediatric patients are still limited due to the rarity of the disease. We aimed to evaluate the efficacy and safety of transcatheter closure for CCAF with a giant CAA in a pediatric population at a single center. Methods: Medical records of pediatric patients (

Background: Epigallocatechin-3-gallate (EGCG) has exhibited antitumor properties in several types of cancers, including nasopharyngeal carcinoma (NPC), but the molecular mechanisms underlying this function remain incompletely understood. The aim of the present study was to characterize the global impact of EGCG on the expression of microRNAs (miRNAs) in NPC cells. Methods: Using microarray analysis, the alterations of miRNA expression profiles were investigated in EGCG-treated CNE2 cells. Furthermore, the target genes and signaling pathways regulated by EGCG-specific miRNAs were identified using target prediction program and gene ontology analysis. Results: A total of 14 miRNAs exhibited >2-fold expression changes in a dose-dependent manner after treatment with 20 μmol/L and 40 μmol/L EGCG. Totally 43, 49, and 52 target genes from these differentially expressed miRNAs were associated with the apoptosis, cell cycle regulation, and cell proliferation, respectively. A total of 66 signaling pathways, primarily involved in cancer development and lipid and glucose metabolism, were shown to be regulated by EGCG-specific miRNAs. Conclusion: EGCG induces considerable alterations of miRNA expression profiles in CNE2 cells, which provides mechanistic insights into cellular responses and antitumor activity mediated by EGCG.

Background: The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. Methods: Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan–Meier were used to analyze the differences between two group or three groups. Results: NRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. Conclusion: Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy.

Background: Enhanced recovery after surgery (ERAS) protocols or fast-track (FT) programs enable a shorter hospital stay and lower complication rate. Minimally invasive surgery (MIS) is associated with a lesser trauma and a quicker recovery in many elective abdominal surgeries. However, little is known of the safety and effectiveness made by ERAS protocols combined with MIS for gastric cancer. The purpose of this study was to evaluate the safety and effectiveness made by FT programs and MIS in combination or alone. Methods: We summarized an 11-year experience on gastric cancer patients undergoing elective laparotomy or minimally invasive gastric resection in standard cares (SC) or FT programs during January 2004 to December 2014. A total of 984 patients were enrolled and assigned into four groups: open gastrectomies (OG) with SC (OG + SC group, n = 167); OG with FT programs (OG + FT group, n = 277); laparoscopic gastrectomies (LG) with FT programs (LG + FT group, n = 248); and robot-assisted gastrectomies (RG) with FT programs (RG + FT group, n = 292). Patients' data were collected to evaluate the clinical outcome. The primary end point was the length of postoperative hospital stay. Results: The OG + SC group showed the longest postoperative hospital stay (mean: 12.3 days, median: 11 days, interquartile range [IQR]: 6–16 days), while OG + FT, LG + FT, and RG + FT groups recovered faster (mean: 7.4, 6.4, and 6.6 days, median: 6, 6, and 6 days, IQR: 3–9, 4–8, and 3–9 days, respectively, all P< 0.001). The postoperative rehabilitation parameters such as flatus time after surgery (4.7 ± 0.9, 3.1 ± 0.8, 3.0 ± 0.9, and 3.1 ± 0.9 days) followed the same manner. After 30 postoperative days' follow-up, the total incidence of complications was 9.6% in OG + SC group, 10.1% in OG + FT group, 8.1% in LG + FT group, and 10.3% in RG + FT group. The complications showed no significant differences between the four groups (all P > 0.05). Conclusions: ERAS protocols alone could significantly bring fast recovery after surgery regardless of the surgical technique. MIS further reduces postoperative hospital stay. It is safe and effective to apply ERAS protocols combined with MIS for gastric cancer.

Background: Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD. Methods: This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training. Results: A total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study. Conclusions: The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks. Trial Registration: ClinicalTrials.gov, NCT01933880; http://clinicaltrials.gov/ct2/show/NCT01933880?term=CONCERTAATT4099&rank=1