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Recurrent somatic mutations in spliceosome factor 3b subunit 1 (SF3B1) are identified in hematopoietic malignancies, with SF3B1-K700E being the most common one. Here, we show that regulatory T cell (T reg )-specific expression of SF3B1-K700E ( Sf3b1 K700Efl/+ /Foxp3 YFP-Cre ) results in spontaneous autoimmune phenotypes. CD4 + T cells from Sf3b1 K700Efl/+ /Foxp3 YFP-Cre mice display defective T reg differentiation and inhibitory function, which is demonstrated by failed prevention of adoptive transfer colitis by Sf3b1 K700Efl/+ /Foxp3 YFP-Cre T regs . Mechanically, SF3B1-K700E induces an aberrant splicing event that results in reduced expression of a cell proliferation regulator Anapc13 due to the insertion of a 231-base pair DNA fragment to the 5' untranslated region. Forced expression of the Anapc13 gene restores the differentiation and ability of Sf3b1 K700Efl/+ /Foxp3 YFP-Cre T regs to prevent adoptive transfer colitis. In addition, acute myeloid leukemia grows faster in aged, but not young, Sf3b1 K700Efl/+ /Foxp3 YFP-Cre mice compared to Foxp3 YFP-Cre mice. Our results highlight the impact of cancer-associated SF3B1 mutation on immune responses, which affect cancer development.

Steroid receptor coactivator (SRC) family members (SRC1, SRC2 and SRC3) are transcriptional co-regulators. SRCs orchestrate gene transcription by inducing transactivation of nuclear receptors and other transcription factors. Overexpression of SRCs is widely implicated in a range of cancers, especially hormone-related cancers. As coactivators, SRCs regulate multiple metabolic pathways involved in tumor growth, invasion, metastasis, and chemo-resistance. Emerging evidence in recent years suggest that SRCs also regulate maturation, differentiation, and cytotoxicity of T cells by controlling metabolic activities. In this review, we summarize the current understanding of the function of SRCs in T cells as well as cancer cells. Importantly, the controversies of targeting SRCs for cancer immunotherapy as well as possible reconciliation strategies are also discussed.

Background: Depression and smoking decrease health status in Chronic Obstructive Pulmonary Disease (COPD), but the combined effect of the two factors is unknown. This study aimed to assess the interactive effects of depression and smoking on the severity of patients with COPD., Methods: A prospective cohort study including 2,268 patients with COPD was conducted in seven rural communities from May 2008 to May 2012. The relationships between the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index and depression and nicotine addiction were assessed. The product of depression and smoking was added to the logistic regression model to evaluate the multiplicative interaction and relative excess risk of interaction (RERI). The Attributable Proportion (AP) of interaction and the synergy index (S) was applied to evaluate the additive interaction of two factors., Results: The severity of COPD in patients with depressive symptoms who never smoked was increased 1.74-fold and in smoking patients it increased by 6.08-fold. Highly addicted smokers with depressive symptoms had a nearly 40-fold increase in severity (all P<0.001). The increased values of the BODE index, HADS-D and Fagerström score also correlated positively (P<0.001). The co-presence of depressive symptoms and smoking significantly increased the BODE index by 11.99-fold with significant biological interactions, relative excess risk of interaction (RERI) was 12.12, the biological interactions were increased with increasing nicotine addiction., Conclusions: Patients with depressive symptoms who also smoke have an increased risk of severity from COPD interaction effects. The risk for severity of COPD and depressive symptoms increased with increasing the severity of nicotine addiction.

Background: A number of effective strategies have been developed to improve the quality of life in patients with COPD. However, few have been implemented in patients with COPD at all stages in a community setting. This study evaluated the efficacy of a complex COPD health management intervention in rural communities in China., Methods: A randomized controlled trial including 8,217 subjects with COPD was implemented from May 2008 to May 2012 in 14 community health-care centers. The control group of subjects received usual care, whereas the management group of subjects participated in a health management program that included assessing the subjects' health status, giving regular health lectures, smoking cessation counseling, encouraging regular exercise, providing rehabilitative training and psychological counseling, and regular follow-up. As a primary outcome, we examined the changes in the BODE index. Secondary outcomes included depression and anxiety rates, current smoking rate, awareness of COPD, mortality, risk factors, respiratory medication use, hospital admissions, and emergency department visits., Results: After 4 y, the mean cumulative value of the BODE index increased by 0.7 per subject in the control group and decreased by 0.4 per subject in the health management group (difference of 1.1, 95% CI 0.2-2.0, P < .001). Health management reduced anxiety symptoms by 4.8%, depression symptoms by 6.6%, current smoking by 14.3%, mortality due to all causes by 9.0%, hospitalizations due to all causes by 16.1%, and emergency department visits due to all causes by 18.1% (P < .05 for all). However, it increased immunomodulator use by 58.9%, respiratory medication use by 14.1-21.9%, and awareness scores for COPD by 57.2% (P < .05 for all)., Conclusions: The health management program is an effective community-based strategy for the prevention and management of COPD in China, increasing awareness and knowledge among patients and practitioners and improving management within the limitations of access to pharmacotherapy., (Copyright © 2015 by Daedalus Enterprises.)

Background: Smoking, depression, and anxiety increase the risk of death in patients with COPD, but the combined effect of these factors is unknown. We assessed the interactive effects of smoking, depression, and anxiety on mortality in patients with COPD., Methods: We collected and analyzed data from 7,787 subjects with COPD, in 14 rural communities, from May 2008 to May 2012, and used logistic regression to evaluate the interactions and relative excess risk due to interaction (RERI). We applied the attributable proportion of interaction and the synergy index to evaluate the additive interactions of the factors., Results: In our COPD subjects the interaction of current smoking and depression symptoms increased the death risk by 3.8-fold (odds ratio 3.78, 95% CI 2.51-5.05), with significant biological interactions (RERI 1.74, 95% CI 0.51-2.99, attributable proportion 0.48, 95% CI 0.13-0.85, synergy index 2.98, 95% CI 1.44-4.56). The biological interactions increased with increasing years or pack-years of smoking: for subjects with ≥ 30 years of smoking: RERI 1.80, 95% CI 1.05-2.75, attributable proportion 0.48, 95% CI 0.15-0.82, synergy index 2.85, 95% CI 1.75-3.96; for subjects with ≥ 40 pack-years of smoking: RERI 3.11, 95% CI 1.54-4.71, attributable proportion 0.60, 95% CI 0.31-0.91, synergy index 4.00, 95% CI 2.84-5.26. Similarly, the combined effect of current smoking and anxiety symptoms increased the death risk by 4.3-fold (odds ratio 4.27, 95% CI 95% CI 2.96-5.59), with significant biological interactions (RERI 1.51, 95% CI 0.31-2.74, attributable proportion 0.46, 95% CI 0.11-0.87, synergy index 2.89, 95% CI 1.31-4.51). The biological interactions also increased with increasing years or pack-years of smoking: for subjects with ≥ 30 years of smoking: RERI 1.41, 95% CI 0.45-2.43, attributable proportion 0.45, 95% CI 0.12-0.81, synergy index 2.88, 95% CI 1.24-5.98; for subjects with ≥ 40 pack-years of smoking: RERI 3.15, 95% CI 2.07-4.61, attributable proportion 0.55, 95% CI 0.21-0.94, synergy index 3.00, 95% CI 1.45-4.75., Conclusions: Smoking, depression, and anxiety are associated with higher risk of death in patients with COPD. The risk of death, depression, and anxiety increases with increasing duration of smoking (years) and cigarette pack-years. Chinese Clinical Trials Registration ChiCTR-TRC-12001958.

Objective: To discuss the role of forehead flap in large external nasal defect reconstruction., Method: We retrospectively reviewed the clinical and follow-up data of 11 patients with large or full-thickness external nasal defects, which were reconstructed with single-or two-stage interpolated or island forehead flaps from January 2007 to June 2011. All patients were male,defects of 9 cases were resulted from resection of skin malignant tumor and traumatic defect in 2 cases. The average diameter of defects was 3.3 cm (2.5-5.0 cm). Four cases had alar full thickness defect. The supratrochlear and angular artery of the elders (>70 yrs) and patients with suspicious peripheral blood vessel lesions were scanned before the surgery by Doppler ultrasonic. The defects were reconstructed by two-stage interpolated flap in 7 cases; five cases were reconstructed by single-stage island flap technique. A nasolabial flap based on piriform aperture was turned into the nasal cavity to reconstruct the lining., Result: All defects were repaired successfully. All tissue flap survived and the scar was not conspicuous. One patient had nostril stenosis with mild nasal congestion complain at the 6th postoperative month., Conclusion: The forehead flap, interpolated or island, can be used safely and effectively to repair the large external nasal defect in experienced hands.

Objective: To determine the dynamic expression of E2F1 in lung of premature rats with hyperoxia-induced chronic lung disease and the relation between E2F1 and pulmonary fibrosis., Methods: Premature Wistar rats at 21 days gestation were randomly and equally divided into a hyperoxia group and a room air group. The hyperoxia group was continuously exposed to hyperoxia (90%) while the air group in room air. Lung tissues in the 2 groups were obtained at 3, 7 and 14 days after exposing to either room air or hyperoxia. The changes of pulmonary histopathology at different time points were observed by hematoxylin and eosin staining; the severity of pulmonary fibrosis was evaluated; and the expression of E2F1 in lung tissue was detected by immunohistochemistry and Western blot., Results: After 3 days of hyperoxia, no significant interstitial fibrosis was observed; while after 7 days in the hyperoxia group, interstitial fibrosis was observed. These changes became more obvious after 14 days of prolonged hyperoxia exposure. No significant difference in the expressions of E2F1 protein was found between the hyperoxia group and the room air group 3 days postnatally (P>0.05). The expression of E2F1 in the hyperoxia group significantly increased 7 days and 14 days postnatally (P<0.05, P<0.01)., Conclusion: Abnormality of E2F1 expression is involved in the pathological process of the proliferation of lung fibroblasts in hyperoxia-induced chronic lung disease neonatal rats, and it plays an important role in lung fibrosis.

Background: Little information is available regarding the vulnerability of patients with chronic obstructive pulmonary disease (COPD) in China. We aimed to assess this according to patient gender., Methods: A cross-sectional study was conducted in the rural area of Xuzhou in China. We interviewed and administered questionnaires to 2825 male and 2825 female patients with COPD and subjected the data generated to statistical analysis. We compared differences between proportions of male and female patients using the χ(2) test., Results: The rate of current smoking in men was 30.1%, whereas that in women was 10.9%, and 31.5% of men had a history of using biomass fuel compared with 75.3% of women. Further, 26.0% of the male patients and 16.4% of the female patients did not take theophylline regularly when their disease was stable. During acute exacerbations, 65.8% of the male patients and 39.7% of the female patients took theophylline or similar drugs. The average potential shortening of life expectancy was 1.76 years for men and 1.18 years for women. The average indirect economic burden was 11158.4 yuan for men and 7481.2 yuan for women. The quality of life was worse in female patients than in male patients., Conclusion: We found that patients with COPD were vulnerable and that factors determining vulnerability were different for men than for women. Therefore, we recommend adopting different measures for men and women when attempting to prevent, control, and treat COPD, rehabilitate these patients, and improve their quality of life.

Objective: To explore a comprehensive surgical approach of genioglossus advancement and hyoid suspension plus uvulopalatopharyngoplasty on the treatment of severe obstructive sleep apnea hypopnea syndrome., Method: Eighteen patients with severe OSAHS (RDI > 40)diagnosed by polysomnography. The obstruction in both the oropharynx and the hypopharynx were determined by preoperative physical examination, fiberoptic pharyngolaryngoscopy, cephalometry, and computed tomography of the upper airway. All the cases were given continuous airway pressure via nose,five to seven days before operation and then were performed genioglossus advancement and hyoid suspension plus uvulopalatopharyngoplasty. The follow up was at least 6 months postoperatively. The Wilcoxon Signed Rank test was used to compare the preoperative and postoperative results by SPSS11.0 for windows., Result: Postoperative 6-24 months, there were statistically significance in all but BMI between preoperative and postoperative measurement. Mean RDI was reduced from preoperative (63.83 +/- 16.34) to postoperative (21.43 +/- 20. 34), lowest mean oxygen saturation increased from (72.44 +/- 7.07)% to (81.33 +/- 13.32)%. According to criterion at home, the 6-month rate of responder is 83.33%. The severe complications such as fracture of the mandible and injure of apex of inferior anterior teeth did not occurred., Conclusion: GAHM plus UPPP is effective surgical approach for patients with severe OSAHS who suffer from oropharyngeal and hypopharyngeal obstruction.

Objective: To discuss the changes of the auditory brain stem response in patients with Ramsay Hunt syndrome., Method: Thirty-six patients of Ramsay Hunt syndrome,who have only unilateral involvement with contralateral good ear, were studied with pure tone test and auditory brain stem response. The latencies of peaks I, III and V and interpeak latencies of I-III, I-V and III-V in bilateral ears were analyzed by SPSS 10.0 for windows., Result: Compared to the controlateral, the affected ears were significantly increased in latencies of II, V and interpeak latencies of I-III, I-V ( P < 0.05)., Conclusion: The audiological data suggested that cochlear or retrocochlear involvement or involvement at more than one site along the auditory pathway existed in Ramsay Hunt syndrome, but pure cochlear hearing loss is not common.

Objective: To explore early post-operative complications following surgery for chronic suppurative otitis media., Method: From Jan 1992 to July 2000, 291 cases of chronic suppurative otitis media have been treated in our department. 79 cases underwent myringoplasty, 82 cases tympanoplasty, 88 cases modified radical mastoidectomy and 42 cases radical mastoidectomy., Result: Facial nerve palsies occurred in 3 cases (1.03%), bone conduction threshold elevation occurred in 13 cases (4.47%), wound infection occurred in 11 cases (3.78%), 7 patients (2.41%) reported symptoms related with chorda tympani trauma, symptoms of jaw discomfort were reported by 7 patients (2.41%) and imbalance or vertigo by 13 patients(4.47%)., Conclusion: The incidence of early complications of surgery for chronic suppurative otitis media in this report was similar to previous reports.