Jun Tai

Genetic polymorphisms in cytochrome P450 genes are associated with an increased risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population.

The purpose of this study was to examine whether functional polymorphisms in the cytochrome P450 (CYP) enzyme genes affect the risk of developing larynx and hypopharynx squamous cell carcinoma (SCC). We investigated CYP1A1, CYP1B1, CYP2E1, and CYP3A4 polymorphisms in 278 patients with laryngeal and hypopharyngeal SCC and 278 control subjects by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with the CYP1A1 3798CC or TC genotype had an odds ratio (OR) of 3.26 (95% confidence interval CI=1.76-6.03) or 1.56 (95% CI=1.06-2.31), compared with those with the TT genotype. An increased risk was also associated with the CYP1A1 462Val/Val genotype (OR=2.39, 95% CI=1.11-5.16), compared with the TT genotype. Haplotype analysis suggested a synergistic effect of these two polymorphisms. A multiplicative joint effect between the CYP1A1 3798T>C polymorphism and smoking was observed. The OR (95% CI) of the TC or CC genotype for nonsmokers and smokers of >20 pack-years were 1.85 (0.99-3.44) or 8.15 (4.35-15.26), respectively (P(trend)<0.05). The CYP1A1 single-nucleotide polymorphisms are associated with an increased risk of developing smoking-related laryngeal and hypopharyngeal SCC in a Han Chinese population.

Knockdown of zinc finger protein, X-linked (ZFX) inhibits cell proliferation and induces apoptosis in human laryngeal squamous cell carcinoma

ZFX (zinc finger protein, X-linked) gene locus on the human X chromosome is structurally similar to the zinc finger protein, Y-linked gene, which may constitute the primary sex-determining signal. However, the pathological roles of the dysfunction of ZFX gene in human disease such as cancer have not been addressed. Here, we analyzed the expression of ZFX in human laryngeal squamous cell carcinoma (LSCC) tissue specimens and found a significant up-regulation compared to corresponding non-tumorous LSCC tissue. Recombinant lentivirus expressing ZFX short hairpin RNA (shZFX) was constructed and infected Hep-2 human LSCC cells. We found that knockdown of ZFX gene resulted in suppression of proliferation and colony-forming ability of Hep-2 cells, and led to S phase cell cycle arrest. In addition, down-regulation of ZFX induced a significant enhancement of cell apoptosis and expression changes of apoptosis-related genes. These results suggest that high expression of ZFX is associated with LSCC progression and knockdown of ZFX may block tumor cell growth mainly by promoting cell apoptosis.

MicroRNA-365a-3p promotes tumor growth and metastasis in laryngeal squamous cell carcinoma

MicroRNAs (miRNAs) are increasingly recognized as oncogenes or tumor suppressors in laryngeal squamous cell carcinoma (LSCC). In this study, we analyzed the roles of miR-365a-3p, miR-143-5p, and miR-494-3p in LSCC using Annexin V/propidium iodide double staining and flow cyto-metry, along with a Transwell migration and invasion assay. The results showed that miR-365a-3p inhibitor significantly facilitated cell apoptosis and suppressed cell cycle progression, migration, and invasion in Hep-2 cells. However, miR-143-5p and miR-494-3p had no such influences. We then investigated the role of miR-365a-3p in LSCC in vivo and found that miR-365a-3p inhibitor suppressed LSCC xenograft tumor growth and metastasis in xenograft mouse models. Moreover, miR-365a-3p inhibitor significantly decreased the expression of p-AKT (Ser473), which indicated that miR-365a-3p can mediate PI3K/AKT signaling pathway transduction via p-AKT (Ser473) in LSCC. The data suggest that miR-365a-3p may act as an oncomiR and may promote growth and metastasis in LSCC via the PI3K/AKT signaling pathway, and thus miR‑365a-3p may be a potential therapeutic target for treatment of LSCC.

Detection of FOXO1 break-apart status by fluorescence in situ hybridization in atypical alveolar rhabdomyosarcoma

The morphologies of alveolar rhabdomyosarcoma (ARMS) are various. Some cases entirely lack an alveolar pattern and instead display a histological pattern that overlaps with embryonal rhabdomyosarcoma (ERMS). The method of pathological diagnosis of ARMS and ERMS has been updated in the 4th edition of the World Health Organization’s guidelines for classification of skeletal muscle tumors. Under the new guidelines, there is still no molecular test to distinguish between these two subtypes of rhabdomyosarcoma (RMS). In the present study, we applied fluorescent in situ hybridization (FISH) and found that the Forkhead box O1 (FOXO1) gene broke apart, amplified, and displayed an aneuploid signal that was related to the RMS pathological subtype. Aside from the fact that FOXO1 break-apart and its amplification were correlated with atypical ARMS, aneuploidies were usually found in atypical ERMS. In conclusion, our results detail a potential biomarker to improve the accuracy of pathological diagnosis by discriminating between atypical ARMS and atypical ERMS.

Correlation between BRAF V600E mutation and clinicopathological features in pediatric papillary thyroid carcinoma

In adults, the presence of the BRAFV600E mutation in papillary thyroid cancer (PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. In contrast, the frequency of this mutation in pediatric PTC has undergone limited study, and the few available estimates range from 0 to 63%. Furthermore, the role of the BRAFV600E mutation in pediatric PTC is controversial; thus, the present study aimed to investigate the prevalence and role of the BRAFV600E mutation in 48 pediatric patients with PTC, aged 3–13 years. Of these patients, 41 were diagnosed with classic PTC, five were found to have a follicular variant of PTC, and two to exhibit a diffuse sclerosing PTC variant. The BRAFV600E mutation was identified to be present in 35.4% of the 48 analyzed patients, and in 41.5% of the patients diagnosed with classical PTC. Furthermore, the presence of the BRAFV600E mutation was found to be associated with a patient age at diagnosis of less than ten years (P=0.011), the performance of a thyroidectomy (P=0.03), exhibited tumor multifocality (P=0.02) and/or extra-thyroidal invasion (P=0.003), and both a low MACIS (Metastases, Age, Completeness of resection, Invasion, Size)(P=0.036) and AMES (Age, Metastasis, Extent of tumor, Size)(P=0.001) score. Together, these data suggest that the presence of the BRAFV600E mutation may be negatively correlated with partial aggressive clinicopathological features of pediatric PTC.

Efficacy and safety of oral sildenafil in treatment of pediatric head and neck lymphatic malformations

Abstract Conclusions: Low dose oral sildenafil citrate tablets are safe and effective to decrease the lesions volume in some LMs children, especially with macrocystic lesion or mixed type. Objective: To evaluate the efficacy and safety of oral sildenafil in treatment of pediatric head and neck lymphatic malformations (LMs). Subjects and methods: In this open-label study, 21 children diagnosed with LMs were given oral sildenafil and stopped at week 24. Volume change of lesions compared with baseline was used to evaluate therapeutic outcome. The improvement of various symptoms and the adverse effects of sildenafil were recorded during the follow-up period. Results: Eight patients (38.0%) showed excellent improvement (>75–100%), one patient (4.8%) had good (>50–75%), two patients (9.6%) had fair (>25–50%), three patients (14.3%) had minimal (0–25%), and seven patients (33.3%) had no improvement. The snoring or stridor completely disappeared in two subjects, although there was no apparent decrease in LMs size. Moreover, all three patients with macrocystic lesions displayed a positive response to sildenafil treatment, followed by mixed type (9/12, 75%). Only two out of six patients with microcystic lesions had minimal clearance. Only four patients showed transient mild diarrhea, there was no other adverse effect in this series.

Pneumomediastinum Secondary to Foreign Body Aspiration: Clinical Features and Treatment Explorement in 39 Pediatric Patients

Background:Pneumomediastinum (PM) secondary to foreign body aspiration (FBA) is rare in children. Although it is mainly benign, some cases may be fatal. Due to the rare nature of this clinical entity, proper assessment and management have been poorly studied so far. Here, we characterized the presentation and management of this clinical entity and provided an evaluation system for the management. Methods:We retrospectively reviewed children with PM secondary to FBA, who were treated in Beijing Childrens Hospital from January 2010 to December 2015. All patients were stratified according to the degree of dyspnea on admission, and interventions were given accordingly. Bronchoscopic removals of airway foreign bodies (FBs) were performed on all patients. For patients in acute respiratory distress, emergent air evacuation and/or resuscitations were performed first. Admission data, interventions, and clinical outcomes were recorded. Results:A total of 39 patients were included in this study. The clinical severity was divided into three grades (Grades I, II, and III) according to the degree of dyspnea. Thirty-one patients were in Grade I dyspnea, and they simply underwent bronchoscopic FBs removals. PM resolved spontaneously and all patients recovered uneventfully. Six patients were in Grade II dyspnea, and emergent drainage preceded rigid bronchoscopy. They all recovered uneventfully under close observation. Two exhausted patients were in Grade III dyspnea. They died from large PM and bilateral pneumothorax, respectively, despite of aggressive interventions in our hospital. Conclusions:PM secondary to FBA could be life-threatening in some patients. The degree of dyspnea should be evaluated immediately, and patients in different dyspnea should be treated accordingly. For patients in Grade I dyspnea, simple bronchoscopic FBs removals could promise a good outcome. For patients in Grade II dyspnea, emergent air evacuation and/or resuscitation should precede a bronchoscopy before the children become exhausted.

Impaired T Cell-dependent Humoral Immune Response Associated with Juvenile-onset Recurrent Respiratory Papillomatosis Progression

Whether humoral immunity plays a role in HPV type 6 or 11 virus-mediated Juvenile-onset Recurrent Respiratory Papillomatosis (JORRP) remains unknown. In the present study, serum total IgG level in 44 JORRP patients was significantly decreased compared with that in 40 healthy controls. Moreover, expanded CD3−CD19+ B cells with down-regulation of CD23, CD40, HLA-DR and up-regulation of CD86 expression were found in the peripheral blood of JORRP patients. Flow cytometry analysis of B-cell compartment showed that the frequency of both CD19+CD27hi plasma cells and CD19+CD27+ memory B cells were decreased in JORRP patients. Importantly, although the proportion of circulating CXCR5+PD1hi Tfh cells was not changed, the function of Tfh cells were greatly impaired with reduced ability of IL-21 secretion to promote B cell maturation. Association analysis by the Kaplan-Meier method revealed that IL-21 secreting Tfh cell was positively correlated to the CD27+ B cell subset frequency, the serum IgG level and the frequency of recurrence in JORRP patients, but negatively correlated to the percentage of IgD+CD27− B cell. We concluded that a reduced IL-21 secretion by Tfh cells may limit B cell maturation and antibody production in JORRP patients and Tfh cell-derived IL-21 might be associated with JORRP outcome in clinic.

Up-regulated lipocalin-2 in pediatric thyroid cancer correlated with poor clinical characteristics

BackgroundThe incidence of thyroid cancer is fast increasing in both adults and children. The pediatric thyroid cancer had often already progressed to a more advanced stage of the disease at diagnosis. Early detection of pediatric thyroid cancer has been a problem for many years. Lipocalin-2 (Lcn2) has been reported to be over-expressed in cancers of diverse histological origin and it facilitates tumorigenesis by promoting survival, growth, and metastasis.MethodsThe plasma Lcn2 concentration of 28 Chinese papillary thyroid cancer (PTC) children and 24 healthy controls was measured. Immunostaining for Ki-67 of tumor tissue from PTC children was performed. The expression levels of Lcn2 and NFκB in PTC tissue and peri-carcinoma tissue of PTC children were measured through Western blot.ResultsThe plasma concentration of Lcn2 was significantly elevated in pediatric PTC patients compared with healthy controls. Besides, the plasma Lcn2 concentration significantly correlated with clinical characteristics, NFκB level, and Ki-67 positive rate of nucleus in tissue of PTC.ConclusionThis is the first study to evaluate the plasma Lcn2 in pediatric PTC patients. It is possible that the plasma Lcn2 may be a new biomarker of pediatric thyroid cancer. Further studies are needed to explore the definite role and mechanism of Lcn2 in thyroid cancer, which will help to explore novel diagnostic or therapeutic strategies.

Sleep Duration and Factors Related to Sleep Loss in 3–14-Year-Old Children in Beijing: A Cross-Sectional Survey

Background: It is known that short sleep duration adversely affects childrens behavior and physical development. This study aimed to investigate the status of sleep duration in 3–14-year-old children in Beijing and explore the related factors of sleep loss with them. Methods: In this study, a cross-sectional study of random stratified cluster sampling was conducted on 3–14-year-old children and adolescents in Beijing. According to the proportion of children in each district and school, the final cohort included a total of 11 kindergartens, 7 primary schools, and 8 junior high schools from 7 districts of Beijing. Children of sampled classes were included, and their parents were invited to fill a series of questionnaires including the simplified Chinese version of Pediatric Sleep Questionnaire, Sleep Questionnaire Scale, and Hong Kong-Children Sleep Questionnaire about the performance of the last 6 months. Results: Out of the total 11,420 questionnaires, 9198 questionnaires were valid and effective with the response rate of 80.54%. The age of the investigated children was 8.8 ± 3.8 years, including 4736 males and 4462 females. The daily sleep duration of children in Beijing was 9.7 ± 0.7 h. The prevalence of sleep loss (<9 h/day) of children in Beijing was 11.8%. The daily sleep duration of children aged <6, 6 ⩽ age <11, and ≥11 years was 9.7 ± 0.6 h, 9.6 ± 0.6 h, and 9.5 ± 0.8 h, respectively. The sleep duration reduced significantly in children aged ≥11 years as compared to younger children in Beijing which was mainly contributed by the variation tendency of sleep duration on weekdays. The multivariate logistic regression analysis identified factors associated with sleep loss (P < 0.05): male (odds ratio [OR] = 1.32, 95% confidence interval [CI]: 1.15–1.51), age ≥11 years (OR = 2.37, 95% CI: 1.92–2.93), overweight (OR = 1.34, 95% CI: 1.17–1.54), family history of snoring (OR = 1.35, 95% CI: 1.13–1.61) and activities before bedtime with watching TV (OR = 1.24, 95% CI: 1.08–1.43), sports (OR = 1.22, 95% CI: 1.01–1.48), playing cellphone (OR = 1.91, 95% CI: 1.31–2.73) and surfing the Internet (OR = 1.27, 95% CI: 1.06–1.52) and among them age ≥11 years and playing cellphone before bedtime had greater impact on childrens short sleep duration than that of other factors. Conclusions: Sleep loss was common among 3–14-year-old children in Beijing. Sleep duration decreased with age, especially among children over 11 years old. Factors associated with sleep loss covered sociodemographic characteristics, family sleep habits and routine activities before bedtime, and among those variables, age ≥11 years and playing with cellphones before bedtime had a greater impact on sleep duration, indicating that existing sleep loss in 3–14-year-old children could be, at least partly, improved by paying more attention to children aged of 11 years or entering Grade 5 and Grade 6 and to children with a family history of snoring; by reducing the use of electronic products before bedtime, especially cellphones; by managing weight and keeping fit; and by improving the bedtime routine.