Extrarenal Wilms tumor with hypertension and dilated cardiomyopathy in an infant: A report of an unusual case.

While Wilms tumors are the most frequently detected kidney cancer type in children, extrarenal Wilms tumors (ERWTs) remain rare. This report is the first to describe hypertension and dilated cardiomyopathy in a patient with an ERWT. A 6-month-old male infant presented with an abdominal mass and paroxysmal hypertension; echocardiography revealed dilated cardiomyopathy with an ejection fraction of 34%, as well as substantially increased plasma renin activity. Pathology yielded a definitive diagnosis of ERWT. Cardiac function and blood pressure gradually returned to normal after tumorectomy. The early diagnosis of such a tumor together with efficient oncologic treatment are vital to optimal patient outcomes.

Association between severity of cardiac dysfunction caused by ventricular pre-excitation-led dyssynchrony and cardiac function recovery after ablation in children.

OBJECTIVE: To investigate the association between the severity of cardiac dysfunction caused by ventricular pre-excitation-led dyssynchrony and cardiac function recovery time after catheter ablation and identify predictors of cardiac function recovery after ablation. METHODS AND RESULTS: A total of 49 children underwent successful ablation (median 2.92 years). This study included 23 patients with mild cardiac dysfunction (left ventricular ejection fraction [LVEF]: 45% ≤ LVEF ≤ 55%), 15 with moderate (30% ≤ LVEF < 45%), and 11 with severe (LVEF <30%). The time for mean LVEF reaching 55% was 0.75, 3, and more than 12 months, respectively. The mean LVEF of children with severe cardiac dysfunction aged ≤6 years normalized within 12 months of follow-up (63.00% ± 1.41%). Mean LVEF of those aged more than 6 years did not normalize at 12 months of follow-up (38.67% ± 10.97%). LVEF recovery time was significantly different between these two age groups (median 11 months vs >12 months, χ2 = 4.55; P = .04). Cox regression analysis showed that preablation smaller left ventricular diastolic diameter (LVDd) Z score and higher LVEF were predictors of cardiac dysfunction recovery time (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.82-0.99, P = .04; HR = 1.09, 95% CI = 1.03-1.15, P = .01). CONCLUSION: Patients with higher LVDd Z scores and lower LVEF tend to have slower improvement in cardiac function after ablation. Patients with LVEF less than 30% and aged more than 6 years need more than 12 months to fully recover, and some might not even completely recover. Early catheter ablation is suggested once ventricular pre-excitation-led cardiac dysfunction is suspected.

Electrophysiological Characteristics and Outcomes of Radiofrequency Catheter Ablation of Atrial Flutter in Children with or Without Congenital Heart Disease.

There are scarce studies on radiofrequency catheter ablation (RFCA) of atrial flutter (AFL) in the pediatric population. This study therefore aimed to investigate the clinical features and RFCA of AFL in children with or without congenital heart disease. Data from 72 consecutive children (44 males; mean age, 6.1 ± 3.8 [0.9-15.0] years; and mean weight, 23.6 ± 13.9 [8.1-72.0] kg) undergoing RFCA for AFL from 2009 to 2019 were retrospectively reviewed. Thirty-three patients had normal cardiac structure and 39 had congenital heart disease (CHD) of whom 29 had undergone surgical repair and developed AFL at a mean of 3.1 ± 2.5 years later. Fifty-nine patients (84%) presented with persistent AFL. Five patients (7%) had cardiac dysfunction with LVEF of 30-48%, which normalized after ablation. Overall, acute success rate of ablation was 99% and recurrence rate was 18% at 0.5-10 years of follow-up. No procedure-related complications were identified. All 33 patients with normal cardiac structure had cavotricuspid isthmus (CTI)-dependent AFL. Among patients who had undergone corrective surgery for CHD, 15 (52%) had CTI-dependent AFL, 4 (14%) had surgical incisional scar reentrant AFL and the remaining 10 (34%) had both CTI-dependent and scar reentrant AFL. Success rate (100% vs. 97%, P = 1.0000) and recurrence rate (21% vs. 16%, P = 0.7008) were similar between patients with and without CHD. Overall, sick sinus syndrome (SSS) was found in 42% (30/72) of patients with AFL, with an incidence of 39% (13/33) among patients with normal cardiac structure and 59% (17/29) among those who underwent surgery for congenital defects. Permanent pacemakers (PM) were implanted in 53% (16/30) of patients with SSS after ablation. RFCA therefore appeared efficacious and safe for treatment of pediatric AFL. The mechanisms underlying AFL after corrective surgery for CHD are complex, including CTI-dependent macro-reentrant, scar reentrant, or a combination of both. SSS is not rare among pediatric AFL cases, with approximately half of patients needing PM implantation.

Right Atrial Appendage Aneurysm Resection to Cure Aneurysm-Related Atrial Tachyarrhythmia.

Congenital right atrial appendage aneurysm (RAAA) is an extremely rare malformation that can coexist with atrial tachyarrhythmia. There is no consensus on treatment for this condition. This research aimed to investigate the clinical characteristics and efficacy of surgical resection to treat atrial tachyarrhythmia originating from RAAA in children. Four RAAA children diagnosed with atrial tachyarrhythmia at the age of 1-5.25 years weighing 8.3-17.1 kg were discussed in this retrospective study. Patients underwent various treatments, included electrocardiogram (ECG) and echocardiography, antiarrhythmic medication therapy, radiofrequency catheter ablation (RFCA), surgical resection of RAAA and pathological examinations. The results from these treatments along with clinical features of patients were analyzed. The incidence of RAAA in patients with atrial tachycardia originating from the right or left atrial appendages (RAA or LAA) was 7.3% (4/55). The prevalence of RAAA in the RAA was 12.5% (4/32). Atrial tachyarrhythmia was identified both prenatally (26 and 36 weeks of gestational age) and postnatally (1 and 4 months after birth), with two patients per group, respectively. The RAAAs condition in two patients with atrial tachycardia (AT), concomitant atrial flutter (AF) and atrial fibrillation (Af) was identified using echocardiogram. Although, RAAA in two patients with mono AT was unidentified in echocardiogram and failed to be identified in the procedure of RFCA, RAAA was confirmed during surgical resection of the RAA. Multiple pre-surgical antiarrhythmic medications combined therapy used to treat all four patients showed either no effect at all or was only partially effective. The original atrial tachyarrhythmia was successfully abolished after RAAA surgical resection in four patients. AT originating from new foci was established in two patients post-surgically. The conditions of these two patients were successfully reverted and normal sinus rhythm maintained in the application of antiarrhythmic medications. These results confirmed the efficacy of RAAA surgical resection. The pathology study showed cystic dilation in parts of the atrial cavity, fibrosis of the cyst wall, generalized fibrosis of atrial myocardium with myocardium atrophy and cystic dilation. RAAA is prone to misdiagnosis by echocardiogram. Atrial tachyarrhythmia in patients with RAAA is usually resistant to antiarrhythmic medication therapy and RFCA. Surgical resection of RAAA is a safe and effective option that is minimally invasive.

Emergency Pacing via the Umbilical Vein and Subsequent Permanent Pacemaker Implantation in a Neonate.

A dying neonate with congenital complete atrioventricular block underwent an emergency temporary pacing via the umbilical vein 1 h after birth. Implantation of a permanent epicardial pacemaker system was performed at the age of 10 days. During the follow-up period of 3 months, the child had been growing well with the VVIR pacemaker.

Nomograms to predict survival after colorectal cancer resection without preoperative therapy.

BACKGROUND: The predictive accuracy of the American Joint Committee on Cancer (AJCC) stages of colorectal cancer (CRC) is mediocre. This study aimed to develop postoperative nomograms to predict cancer-specific survival (CSS) and overall survival (OS) after CRC resection without preoperative therapy. METHODS: Eligible patients with stage I to IV CRC (n = 56072) diagnosed from 2004 to 2010 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were allocated into training (n = 27,700), contemporary (n = 3158), and prospective (n = 25,214) validation cohorts. Clinically important variables were incorporated and selected using the Akaike information criterion in multivariate Cox regressions to derive nomograms with the training cohort. The performance of the nomograms was assessed and externally testified using the concordance index (c-index), bootstrap validation, calibration, time-dependent receiver-operating characteristic curves, Kaplan-Meier curves, mosaic plots, and decision curve analysis (DCA). Performance of the conventional AJCC stages was also compared with the nomograms using similar statistics. RESULTS: The nomograms for CSS and OS shared common predictors: sex, age, race, marital status, preoperative carcinoembryonic antigen status, surgical extent, tumor size, location, histology, differentiation, infiltration depth, lymph node count, lymph node ratio, and metastasis. The c-indexes of the nomograms for CSS and OS were 0.816 (95 % CI 0.810-0.822) and 0.777 (95 % CI 0.772-0.782), respectively. Performance evaluations showed that the nomograms achieved considerable predictive accuracy, appreciable reliability, and significant clinical validity with wide practical threshold probabilities, while the results remained reproducible when applied to the validation cohorts. Additionally, model comparisons and DCA proved that the nomograms excelled in stratifying each AJCC stage into three significant prognostic subgroups, allowing for more robust risk classification with an improved net benefit. CONCLUSIONS: We propose two prognostic nomograms that exhibit improved predictive accuracy and net benefit for patients who have undergone CRC resection. The established nomograms are intended for risk assessment and selection of suitable patients who may benefit from adjuvant therapy and intensified follow-up after surgery. Independent external validations may still be required.

Effectiveness of Radiofrequency Catheter Ablation of Outflow Tract Ventricular Arrhythmias in Children and Adolescents.

Outflow tract ventricular arrhythmias (OTVAs) are common in children; however, experience is limited on their radiofrequency catheter ablation (RFCA). The purpose of this study was to assess the outcomes of mapping and ablation of pediatric OTVAs and to evaluate the role of ECG algorithms in distinguishing the origin of OTVAs. We compared retrospectively collected single-center data on 92 consecutive pediatric patients (58 male; age, 8.2 ± 2.9 [range 3.6-18] years) who underwent RFCA for OTVAs from 2009 to 2015. Two independent and blinded observers analyzed ECG data. Of these children, 69 (75 %) were of RVOT origin. RFCA was given up in 1 case, and the acute success rate was 92.3 % (84/91), the 1-year follow-up recurrence rate was 8.3 % (7/84) and the complications of the procedure were 2.2 % (2/92). And 3D versus 2D mapping-guided RFCA was associated with significantly (p < 0.05) higher acute success rate (96.1 % [49/51] vs. 87.5 % [35/40]), and lower X-ray exposure (742.5 ± 323.1 vs. 1432.3 ± 605.5 mGy cm2) and 1-year recurrence rate (4.1 % [2/49] vs. 14.3 % [5/35]). The positive predictive value of four types of ECG algorithms used in adults for LVOT origin was only 47.7-65.4 %. In these cases, four identified as RVOT origin and two identified as LVOT origin by ECG underwent successful ablation on the other side of outflow tract finally. And these six children who underwent successful RFCA in both sides of outflow tract had no follow-up recurrence. OTVAs in children originate mostly from RVOT. RFCA can be used for ablation of pediatric OTVAs effectively and safely. In some cases, successful RFCA should be ablated in both sides of outflow tract. ECG-based prediction of OTVA origin as used in adults is limited in children.

Optimal noninvasive assessment of initial left ventricular dysfunction in children with ectopic atrial tachycardia.

UNLABELLED: Tissue Doppler imaging (TDI) can identify cardiac dysfunction in adults. This study is aimed to improve early identification of initial left ventricular (LV) dysfunction secondary to ectopic atrial tachycardia (EAT) in children by TDI. A total of 70 children with EAT were included in the present study. Cardiac function was evaluated by conventional echocardiography, TDI, and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP). Doppler signals obtained from the mitral inflow and TDI of the mitral annulus were the average values of three consecutive heartbeats. Left ventricular ejection fraction (LVEF), peak early diastolic transmitral velocity (E), peak systolic mitral annulus velocity (S'), early diastolic mitral annular velocity (E'), the ratio E/E', and TDI-derived myocardial performance index (TDI-MPI) were compared between two groups of children with normal or elevated plasma NT-proBNP concentrations. Of the children, 18.6% demonstrated tachycardia-induced cardiomyopathy (TIC). Compared with LVEF, the TDI-MPI and E/E' showed better correlations with elevated plasma NT-proBNP. Addition of TDI-MPI and E/E' to LVEF provided increased information to detect elevated plasma NT-proBNP (91.67% sensitivity). CONCLUSIONS: TIC occurred in 18.6% of children with EAT. Initial LV dysfunction assessed by the TDI-MPI and E/E' is associated with elevated plasma NT-proBNP, even the LVEF is normal.

Meta-analysis shows that circulating tumor cells including circulating microRNAs are useful to predict the survival of patients with gastric cancer.

BACKGROUND: Circulating tumor cells (CTCs) are metastatic cells disseminated into the bloodstreams. They have been proposed to monitor disease progression for decades. However, the prognostic value of CTCs in gastric cancer (GC) remains controversial. We performed a meta-analysis to investigate the topic. METHODS: A systematic search was made for relevant studies in academic data bases, involving the Medline, Embase, and Science Citation Index. Data on prognosis of GC patients, such as recurrence-free survival (RFS) and overall survival (OS), were extracted when possible. The meta-analysis was performed with the random effects model and the pooled hazard ratios (HRs) and their associated 95% confident intervals (95%CIs) were computed as effect measures. RESULTS: Twenty six studies (including 40 subgroups) with peripheral blood samples of 1950 cases from 10 countries were included in the final analysis. The pooled results showed that GC patients with detectable CTCs (including circulating miRNAs) had a tendency to experience shortened RFS (HR=2.91, 95% CI [1.84-4.61], I2=52.18%, n=10). As for patient deaths, we found a similar association of CTC (including circulating miRNAs) presence with worse OS (HR=1.78, 95% CI [1.49-2.12], I2=30.71%, n=30). Additionally, subgroup analyses indicated strong prognostic powers of CTCs, irrespective of geographical, methodological, detection time and sample size differences of the studies. CONCLUSIONS: Our meta-analysis shows that CTCs (including circulating miRNAs) can predict the survival of GC patients. Large prospective studies are warranted to determine the best sampling time points, detection methods in homogeneous patients with GC in the future.

FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells.

AIM: Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC), and the underlying mechanism remains unclear. FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients. In this study, we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms. METHODS: Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used. mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis. RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells, and lentiviral infection was used to overexpress FoxM1 in H292 cells. MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells. RESULTS: Treatment of SPC-A-1 cells with gefitinib (1 and 10 µmol/L) upregulated the expression of FoxM1 in time- and concentration-dependent manners, while gefitinib (1 µmol/L) downregulated in H292 cells. In SPC-A-1 cells treated with gefitinib (1 µmol/L), the expression of several downstream targets of FoxM1, including survivin, cyclin B1, SKP2, PLK1, Aurora B kinase and CDC25B, were significantly upregulated. Overexpression of FoxM1 increased the resistance in H292 cells, while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis. CONCLUSION: The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro. FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

Bis(µ-3,5-dimethyl-4H-1,2,4-triazol-4-amine-κN:N)bis-[bis-(thio-cyanato-κN)zinc]-bis-(3,5-dimethyl-4H-1,2,4-triazol-4-amine-κN)bis-(thio-cyanato-κN)zinc (1/2).

In the crystal structure of the title 1:2 adduct, [Zn(2)(NCS)(4)(C(4)H(8)N(4))(2)]·2[Zn(NCS)(2)(C(4)H(8)N(4))(2)] or (Ia)·2(Ib), each Zn(II) atom is coordinated in a distorted tetra-hedral geometry by four N atoms from two triazole rings of two 4-amino-3,5-dimethyl-1,2,4-triazole (admt) ligands and two NCS(-) ligands. In (Ia), double N(1):N(2)-bridging admt ligands connect two Zn(II) atoms, forming a dimer with a Zn(2)(admt)(2) six-membered metallacycle located on a crystallographic inversion center. In (Ib), the admt ligands exhibit monodentate N(1)-coordination modes. Weak N-H⋯N, N-H⋯S and C-H⋯S hydrogen bonds play an important role in the inter-molecular packing. The S and C atoms of two thiocyanato ligands are disordered over two sets of sites in ratios of 0.57 (3):0.43 (3) and 0.63 (3):0.37 (3), respectively.

Ethyl 2-methyl-4-phenyl-pyrido[1,2-a]benzimidazole-3-carboxyl-ate.

The title compound, C(21)H(18)N(2)O(2), was synthesized using a novel tandem annulation reaction between (1H-benzimidazol-2-yl)(phen-yl)methanone and (E)-ethyl 4-bromo-but-2-enoate under mild conditions. The dihedral angles between the mean planes of the five-membered imidazole ring and the pyridine, benzene and phenyl rings are 0.45 (6), 1.69 (1) and 70.96 (8)°, respectively. In the crystal, mol-ecules are linked through inter-molecular C-H⋯N hydrogen bonds.

Three-dimensional laparoscopy-assisted bowel resection for cavernous hemangioma of the rectum: Report of two cases.

The safety and feasibility of 3-D laparoscopy-assisted bowel resection were demonstrated in the management of rectal cancer. However, this procedure's role in the management of patients with diffuse cavernous hemangioma of the rectum has not been evaluated. Here, two patients were diagnosed with diffuse cavernous hemangioma of the rectum by colonoscopy and abdominal imaging. One case underwent pull-through transection and coloanal anastomosis in 3-D laparoscopy-assisted surgery. In another patient, 3-D laparoscopy-assisted abdominoperineal resection was performed. The operations were safely performed in both cases. The two patients recovered uneventfully, and satisfactory postoperative outcomes were demonstrated. This report shows that 3-D laparoscopy-assisted bowel resection may be safe and feasible for patients with diffuse cavernous hemangioma of the rectum.

Mesenteric injection of adipose-derived mesenchymal stem cells relieves experimentally-induced colitis in rats by regulating Th17/Treg cell balance.

Efficient delivery routes are critical for the effectiveness of adipose-derived mesenchymal stem cells (ADMSCs) in treating inflammatory bowel disease (IBD). Conventional ADMSC delivery routes include local, intravenous and intraperitoneal injection. Whether mesenteric injection has potential in IBD treatment remains unknown. In the present study, we investigated the therapeutic effects of mesenteric injection of ADMSCs in a trinitrobenzene sulfonic acid-induced rat IBD model and explored whether this treatment affected T helper 17 (Th17)/regulatory T (Treg) cell ratio. The results showed that mesenteric injection of ADMSCs markedly reduced signs of colitis, colon shortening, weight loss and pathological damage. The treatment also decreased serum tumor necrosis factor alpha concentration, increased serum tumor necrosis factor alpha-stimulated gene protein 6 concentration, and augmented repair via proliferation (assessed by evaluating Ki-67 levels) in colonic tissue. Moreover, mesenteric injection of ADMSCs reduced interleukin (IL)-17A and IL-6 mRNA expression, and increased IL-10 and transforming growth factor-beta mRNA expression in colonic tissue. Protein analyses indicated that mesenteric injection of ADMSCs was associated with increased expression of forkhead box P3+ and IL-10 as well as decreased expression of retinoid-related orphan receptor λt and IL-17. Additionally, the treatment inhibited phosphorylation of signal transducer and activator of transcription (STAT) 3 and activated phosphorylation of STAT5. Taken together, these results suggest that mesenteric injection of ADMSCs is a promising approach to treating trinitrobenzene sulfonic acid-induced IBD, and achieves its therapeutic effect by regulating the pro/anti-inflammatory Th17/Treg cell balance.

Characteristics of circular RNA expression in lung tissues from mice with hypoxia­induced pulmonary hypertension.

Pulmonary hypertension (PH) is a life­threatening lung disease, characterized by an increase in pulmonary arterial pressure caused by vasoconstriction and vascular remodeling. The pathogenesis of PH is not fully understood, and there is a lack of potential biomarkers for the diagnosis and treatment of patients with PH. Non­coding RNAs with a characteristic covalently closed loop structure, termed circular RNAs (circRNAs), are present in a number of pulmonary diseases. To the best of our knowledge, the present study is the first to use microarray analysis to determine the expression profile of circRNAs in lung tissues from mice with hypoxia­induced PH. In total, 23 significantly upregulated and 41 significantly downregulated circRNAs were identified. Of these, 12 differentially expressed circRNAs were selected for further validation using reverse transcription­quantitative polymerase chain reaction. Putative microRNAs (miRNAs) that bind to the dysregulated circRNAs were predicted. Subsequently, bioinformatics tools were used to construct circRNA­miRNA­mRNA networks for the two most promising circRNAs, namely mmu_circRNA_004592 and mmu_circRNA_018351. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of target genes of the dysregulated circRNAs revealed that these dysregulated circRNAs may serve an important role in the pathogenesis of hypoxia­induced PH. Therefore, these dysregulated circRNAs are candidate diagnostic biomarkers and potential therapeutic targets for PH.

Tumor deposit is an independent prognostic indicator in patients who underwent radical resection for colorectal cancer.

Background: Tumor deposits are one of the promising factors among the different edition of Tumor, Node, Metastasis classification. Despite improvement in the treatment of various types of metastatic disease the source and prognostic significance of tumor deposits in staging has not been deliberating the agreeable opinion. We investigated the possibility of tumor deposit as independent prognostic factor and evaluating its prognostic value in colorectal carcinoma patients. Methods: Author studied 313 colorectal cancer patients clinocopathological data and outcome who underwent radical resection. Data between 2011-2015 were retrospectively collected from Shanghai East Hospital, affiliated with Tongji University data information centre. The analysis was used to calculate 2 years disease free survival(DFS) and relation of tumor deposit with number of lymph node positive. Cox-regression analysis was performed to assess the prognostic factor. Results: Out of 313 colorectal patients included in the study, tumor deposits were detected in 17%. Tumor deposits (TDs) are relevantly associated with significant poor outcomes. The tumor deposit were significantly correlated with T-stage(P=<0.001), N-stage(P=<0.001), PLNC(P=<0.001), venous invasion(P=<0.001), TNM staging(P=<0.001), CEA(P=0.021) and CA19-9(P=0.042) of primary tumor. The Kaplan-Meier analysis revealed that disease-free survival of CRC patients with positive tumor deposit were significantly poorer that those with negative tumor deposit cohort(P=<0.001) And with multivariate analysis in different model, we found that positive tumor deposit were significantly associated with shorter DSF which is totally independent with lymph node status (P=0.001 and P=0.023 respectively). Subgroup analysis found that of 179 CRC patients with negative lymph node status, the DFS of patients with positive tumor deposit were significantly shorter that those with negative tumor deposit(P=,0.001). Of 134patients with positive lymph node status, the DFS of patients shows similar result. (P=<0.001). Conclusion: We have shown that TDs are not equal to lymph node metastasis with respect to biology and outcome. Tumor deposits are an independent adverse prognostic factor in CRC patient who have undergone radical resection.

[Cyclin D1 and its association with airway remodeling in a murine model of asthma].

OBJECTIVE: To evaluate the expression of cyclin D(1) in asthmatic mouse lungs, and to explore the role of cyclin D(1) in bronchial asthma and airway remodeling. METHODS: Forty BALB/c mice were randomized to group A (normal), group B (sensitized for 2 weeks), group C (sensitized for 4 weeks) and group D (sensitized for 8 weeks), 10 mice each group. The mice were sensitized with 10% ovalbumin and challenged with 1% ovalbumin to establish the asthmatic model. The number of eosinophils and the cell percentages in bronchoalveolar lavage fluid (BALF) were counted by cytology method. Pulmonary functions were measured to evaluate the resistance of expiration. Airway inflammation and eosinophil infiltration were evaluated by HE staining, and the airway wall thickness (WAt/Pi), smooth muscle thickness (WAm/Pi) and smooth nucleus counts (N/Pi) were quantified by computer-assisted image analysis system. The mRNA expression of cyclin D(1) was measured by RT-PCR and Real-time PCR. The protein expression of cyclin D(1) was assayed by Western blot. The correlation between airway resistance of expiration and the expression of cyclin D(1) was studied. RESULTS: The eosinophil count and differential in BALF of group B, C, and D [(42.6 +/- 0.9) x 10(4)/L, (54.7 +/- 1.4) x 10(4)/L, (44.8 +/- 2.4) x 10(4)/L] were higher than those of group A (3.4 +/- 0.5) x 10(4)/L (q = 79.75, 91.42, 84.82, all P < 0.01). The airway resistance of expiration after challenge with 45 microg/kg acetylcholine in group B, C, and D [(5.27 +/- 0.16) cmxL(-1)xmin(-1), (6.68 +/- 0.20) cmxL(-1)xmin(-1), (7.14 +/- 0.41) cmxL(-1)xmin(-1)] was higher than that in group A [(4.11 +/- 0.15) cmxL(-1)xmin(-1), q = 5.58, 6.39, 7.11, all P < 0.05]. Eosinophil infiltration, cilium loss, formation of mucus plug and smooth muscle cell layer thickening were observed in group B, C, and D. The morphological changes of the airways became evident following airway remodeling. WAm/Pi in group B, C, and D (2.8 +/- 0.6, 4.8 +/- 0.6, 6.4 +/- 0.7) were higher than in group A (2.4 +/- 0.4, q = 6.40, 8.28, 9.27, all P < 0.05), and WAt/Pi in group B, C, and D (6.4 +/- 0.8, 8.3 +/- 1.2, 9.3 +/- 1.0) were higher than in group A (5.6 +/- 1.0, q = 2.80, 4.83, 6.37, all P < 0.05). The protein expression of Cyclin D(1) in group B, C, and D (0.587 +/- 0.015, 0.808 +/- 0.029, 0.826 +/- 0.022) were higher than in group A (0.404 +/- 0.016, q = 5.87, 8.08, 8.26, all P < 0.01). There was a positive correlation between the expression of cyclin D(1) and airway resistance (r = 0.83, P < 0.05). CONCLUSIONS: The expression of cyclin D(1) in the asthmatic mouse lung was increased, and positively correlated to airway reactivity. Cyclin D(1) might be essential in the airway remodeling of asthma through ERK signaling pathway.

The Prognostic Value of Circulating Cell-Free DNA in Colorectal Cancer: A Meta-Analysis.

BACKGROUND: Circulating cell-free DNA (cfDNA) is a promising candidate biomarker for detection, monitoring and survival prediction of colorectal cancer (CRC). However, its prognostic significance for patients with CRC remains controversial. To derive a precise estimation of the prognostic significance of cfDNA, a meta-analysis was performed. METHODS: We made a systematic search in data base of the Science Citation Index Embase and Pubmed for studies reporting prognostic data of cfDNA in CRC patients. The data of cfDNA on recurrences-free survival (RFS) and overall survival (OS) were extracted and measured in hazard rates (HRs) and 95% confident intervals (CIs). Subgroup analyses were carried out as well. Finally, the meta-analysis is accompanied with nine studies including 19 subunits. RESULTS: The pooled HRs with 95% CIs revealed strong associations between cfDNA and RFS (HR [95%CI]=2.78[2.08-3.72], I(2)=32.23%, n=7) along with OS (HR [95%CI]=3.03[2.51-3.66], I(2)=29.24%, n=12) in patients with CRC. Entire subgroup analyses indicated strong prognostic value of cfDNA irrespective tumor stage, study size, tumor markers, detection methods and marker origin. CONCLUSIONS: All the results exhibits that appearance of cfDNA in blood is an indicator for adverse RFS and OS in CRC patients.

A Nomogram to Predict Adequate Lymph Node Recovery before Resection of Colorectal Cancer.

Increased lymph node count (LNC) has been associated with prolonged survival in colorectal cancer (CRC), but the underlying mechanisms are still poorly understood. The study aims to identify new predictors and develop a preoperative nomogram for predicting the probability of adequate LNC (≥ 12). 501 eligible patients were retrospectively selected to identify clinical-pathological factors associated with LNC ≥ 12 through univariate and multivariate logistic regression analyses. The nomogram was built according to multivariate analyses of preoperative factors. Model performance was assessed with concordance index (c-index) and area under the receiver operating characteristic curve (AUC), followed by internal validation and calibration using 1000-resample bootstrapping. Clinical validity of the nomogram and LNC impact on stage migration were also evaluated. Multivariate analyses showed patient age, CA19-9, circulating lymphocytes, neutrophils, platelets, tumor diameter, histology and deposit significantly correlated with LNC (P < 0.05). The effects were marginal for CEA, anemia and CRC location (0.05 < P < 0.1). The multivariate analyses of preoperative factors suggested decreased age, CEA, CA19-9, neutrophils, proximal location, and increased platelets and diameter were significantly associated with increased probability of LNC ≥ 12 (P < 0.05). The nomogram achieved c-indexes of 0.75 and 0.73 before and after correction for overfitting. The AUC was 0.75 (95% CI, 0.70-0.79) and the clinically valid threshold probabilities were between 10% and 60% for the nomogram to predict LNC < 12. Additionally, increased probability of adequate LNC before surgery was associated with increased LNC and negative lymph nodes rather than increased positive lymph nodes, lymph node ratio, pN stages or AJCC stages. Collectively, the results indicate the LNC is multifactorial and irrelevant to stage migration. The significant correlations with preoperative circulating markers may provide new explanations for LNC-related survival advantage which is reflected by the implication of regional and systemic antitumor immune responses.

A nomogram improves AJCC stages for colorectal cancers by introducing CEA, modified lymph node ratio and negative lymph node count.

Lymph node stages (pN stages) are primary contributors to survival heterogeneity of the 7th AJCC staging system for colorectal cancer (CRC), indicating spaces for modifications. To implement the modifications, we selected eligible CRC patients from the Surveillance Epidemiology and End Results (SEER) database as participants in a training (n = 6675) and a test cohort (n = 6760), and verified tumor deposits to be metastatic lymph nodes to derive modified lymph node count (mLNC), lymph node ratio (mLNR), and positive lymph node count (mPLNC). After multivariate Cox regression analyses with forward stepwise elimination of the mLNC and mPLNC for the training cohort, a nomogram was constructed to predict overall survival (OS) via incorporating preoperative carcinoembryonic antigen, pT stages, negative lymph node count, mLNR and metastasis. Internal validations of the nomogram showed concordance indexes (c-index) of 0.750 (95% CI, 0.736-0.764) and 0.749 before and after corrections for overfitting. Serial performance evaluations indicated that the nomogram outperformed the AJCC stages (c-index = 0.725) with increased accuracy, net benefits, risk assessment ability, but comparable complexity and clinical validity. All the results were reproducible in the test cohort. In summary, the proposed nomogram may serve as an alternative to the AJCC stages. However, validations with longer follow-up periods are required.