A Novel Clinical Tool to Detect Severe Obstructive Sleep Apnea.

Purpose: Obstructive sleep apnea (OSA) is a disease with high morbidity and is associated with adverse health outcomes. Screening potential severe OSA patients will improve the quality of patient management and prognosis, while the accuracy and feasibility of existing screening tools are not so satisfactory. The purpose of this study is to develop and validate a well-feasible clinical predictive model for screening potential severe OSA patients. Patients and Methods: We performed a retrospective cohort study including 1920 adults with overnight polysomnography among which 979 cases were diagnosed with severe OSA. Based on demography, symptoms, and hematological data, a multivariate logistic regression model was constructed and cross-validated and then a nomogram was developed to identify severe OSA. Moreover, we compared the performance of our model with the most commonly used screening tool, Stop-Bang Questionnaire (SBQ), among patients who completed the questionnaires. Results: Severe OSA was associated with male, BMI≥ 28 kg/m2, high blood pressure, choke, sleepiness, apnea, white blood cell count ≥9.5×109/L, hemoglobin ≥175g/L, triglycerides ≥1.7 mmol/L. The AUC of the final model was 0.76 (95% CI: 0.74-0.78), with sensitivity and specificity under the optimal threshold selected by maximizing Youden Index of 73% and 66%. Among patients having the information of SBQ, the AUC of our model was statistically significantly greater than that of SBQ (0.78 vs 0.66, P = 0.002). Conclusion: Based on common clinical examination of admission, we develop a novel model and a nomogram for identifying severe OSA from inpatient with suspected OSA, which provides physicians with a visual and easy-to-use tool for screening severe OSA.

Targeting Glutamine Metabolism through Glutaminase Inhibition Suppresses Cell Proliferation and Progression in Nasopharyngeal Carcinoma.

BACKGROUND: Glutaminase (GLS), the key enzyme involved in glutamine metabolism, has been identified as a critical player in tumor growth and progression. The GLS inhibitor CB-839 has entered several clinical trials against a variety of tumors. OBJECTIVE: Our study aimed to investigate the role and underlying mechanism of GLS and its inhibitor CB-839 in nasopharyngeal carcinoma (NPC). METHODS: The expression, downstream genes, and signaling pathways of GLS in NPC were determined by real-time polymerase chain reaction (RT-PCR), PCR array, western blotting (WB), and immunohistochemical staining (IHC), and the phenotype of GLS was confirmed by in vivo experiments of subcutaneous tumor formation in mice and in vitro experiments of functional biology, including Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, transwell migration, and Boyden invasion assay. Finally, it was also verified whether the treatment of NPC cells by GLS inhibitor CB-839 can change various biological functions and protein expression to achieve the purpose of blocking tumor progression. RESULTS: GLS was remarkably overexpressed in NPC cells and tissues, predicting a poor overall survival of NPC patients. GLS promoted cell cycle, proliferation, colony formation, migratory, and invasive capacities by regulating Cyclin D2 (CCND2) via PI3K/AKT/mTOR pathway in NPC in vitro and in vivo. Notably, CB-839 showed an effective anti-NPC tumor effect by blocking the biological functions of the tumor. CONCLUSION: The first innovative proof is that GLS promotes cell proliferation by regulating CCND2 via PI3K/AKT/mTOR pathway in NPC, and GLS inhibitor CB-839 may serve as a new potential therapeutic target for NPC treatment.

Peyer's patch-involved gut microbiota facilitates anti-HBV immunity in mice.

BACKGROUND: Gut microbiota is crucial for immune homeostasis and is associated with the prognosis of chronic hepatitis B infection. Peyer's patches (PPs), characterized by intestinal mucosa localization, are involved in the gut microbiota-mediated immune response. However, whether and how PPs orchestrate gut microbiota-modulated anti-hepatitis B virus (HBV) response remain elusive. This study aims to elucidate the role of PPs in gut microbiota-mediated anti-HBV adaptive immunity. METHODS: We investigated the effects of gut microbiota and PPs on adaptive immune responses by transcriptomic, phenotypic, and functional analyzes from an HBV mouse model with gut commensal microbiota and PP-depleting interventions. RESULTS: Depletion of gut microbiota impaired systemic adaptive immune responses, resulting in a delayed HBV antigen clearance. Differentially expressed genes analysis of PPs revealed that pathways related to adaptive immune responses were significantly downregulated in gut microbiota-deficient mice. Notably, the depletion of PPs could abolish gut microbiota-boosted intrahepatic HBV-specific T cell response, leading to a higher serum hepatitis B surface antigen level in mice. CONCLUSION: PPs orchestrate gut microbiota-mediated intrahepatic anti-HBV cellular immunity, underlining the significance of remote manipulating the "gut microbiota-PPs" axis for achieving optimum anti-HBV response.

Laryngeal contact granuloma after radiotherapy in patients with nasopharyngeal carcinoma: a case series.

Background: Laryngeal contact granuloma (LCG) is a benign hypertrophic lesion and phonatory injury after abnormal vocal behavior is regarded as its major etiology. Patients receiving radiation for non-laryngeal head and neck tumors are troubled by persistent voice impairment. The occurrence of LCG after radiotherapy for nasopharyngeal carcinoma (NPC) in our practice has implored us to re-exam their underlying etiology. We hypothesize that a proportion of LCG results from voice change caused by non-laryngeal head and neck cancer radiotherapy and firstly describe a distinct LCG population originated after radiotherapy for NPC with respect to the clinical profile, presentation, prognosis and response to treatment of patients. Methods: We retrospectively reviewed the laryngoscopic examination and tumor study findings to elucidate the common clinical features of patients who presented with LCG after radiotherapy for NPC. All patients were regularly monitored with telescopic examination until lesions disappeared. Data on age, sex, clinical presentation, telescopic findings, management, latency time of lesion formation, remission time and clinical outcome were reviewed. Results: The medical review identified 27 cases of LCG secondary to radiotherapy for NPC. All lesions had been diagnosed during routine endoscopy following radiation. The interval between radiation onset and endoscopic diagnosis was 3.77 months (range, 0.67-11 months). 20 cases were resolved through simple observation, 4 cases were resolved with the administration of proton pump inhibitors (PPIs), and 3 cases with a poor response to PPI therapy required subsequent surgical resection. The mean remission time in the observation and PPI groups was 4.42 months (range, 0.73-18.9 months) and 5.78 months (range, 2.17-14.63 months), respectively. All patients recovered completely and none experienced recurrence during a mean follow-up of 32.44 months (range, 5.6-71.67 months). Conclusions: Iatrogenic granulomas of vocal process are presenting after radiation for non-laryngeal head and neck cancers. In contrast with spontaneous granulomas, these granulomas can be cured at high remission rates and low recurrence trend without specific intervention. Thus, simple observation may be sufficient for radiation-induced LCG.

[New progress in diagnosis and treatment of HPV-positive oropharyngeal carcinoma].

In recent years, the incidence of oropharyngeal carcinoma （OPC） is increasing, while the better prognosis of patients with Human papillomavirus （HPV） positive oropharyngeal carcinoma has been confirmed in a number of studies. There are a variety of detection methods for HPV-associated oropharyngeal carcinoma. Including P16 immunohistochemistry, Polymerase Chain Reaction （PCR） or In situ hybridization （ISH） detection of HPV DNA, HPV RNA, Revers transcriptase Polymerase Chain Reaction （RT PCR） was used to detect HPV RNA. The better prognosis of patients with HPV-positive oropharyngeal carcinoma has led to the emergence of a large number of degraded treatment trials. The traditional P16 test has certain limitations in the diagnosis of patients with HPV-positive oropharyngeal carcinoma. It is necessary to combine with other detection methods to accurately screen out patients with HPV-positive oropharyngeal carcinoma and better apply to degraded therapy. In this article, we will briefly introduce the trend of HPV-associated oropharyngeal carcinoma, the detection methods and the new progress of degraded treatment trials.

Muscle type of palatopharyngeal muscle in children with severe obstructive sleep apnea.

STUDY OBJECTIVES: To investigate the fiber-type distribution in palatopharyngeal muscle via adenosine triphosphatase and quantitative real-time polymerase chain reaction in children with severe obstructive sleep apnea (OSA). METHODS: Study participants were 12 children with severe OSA and 15 children with simple snoring as the control group. Both groups were diagnosed by polysomnography and treated with tonsillectomy. The samples of palatopharyngeus muscle were studied under adenosine triphosphatase staining and quantitative real-time polymerase chain reaction to classify the different fiber types. RESULTS: There were no differences in baseline age, body mass index, tonsil size, or sleep stage constitution between the 2 groups. Dominance (>60%) of type I fiber was observed both in children with simple snoring (3/15, 20%) and in those with severe OSA (1/12, 8.3%) via adenosine triphosphatase staining. Predominance of type II fibers was seen in 3/15 (20%) in the control group and 6/12 (50%) in the severe OSA group, respectively. Type grouping was also seen in 8/15 (53.3%) in non-OSA and 6/12 (50%) in severe OSA groups, respectively. There was no difference in distribution of subtype fibers assessed by quantitative real-time polymerase chain reaction between the 2 groups; the mean percentages of type I fibers were 25.8% ± 19.5% and 20.9% ± 16.6%, respectively (P > .05), similar to type IIa fibers (35.2% ± 23.4% and 40.9% ± 28.8%) (P > .05). There was a decrease in the percentage of type I fibers between children younger and older than 12 years (P < 0.05), although this was not due to OSA (P > 0.05). CONCLUSIONS: There were no specific changes via adenosine triphosphatase staining or a difference in distribution of subtype fibers via quantitative real-time polymerase chain reaction between children with severe pediatric OSA and those with simple snoring, whereas the percentage of type I fiber decreased dynamically due to age but not OSA. CLINICAL TRIAL REGISTRATION: Registry: Chinese Clinical Trials Registry; Name: A study of the mechanism of the conversion of upper airway expasion muscle's fiver types of OSA patient which may be mediated by estrogen-related receptor alpha; URL: https://www.chictr.org.cn/showproj.aspx?proj=6144; Identifier: ChiCTR-CCC-13003415.

Establishment of Immortalized Laryngeal Epithelial Cells Transfected with Bmi1.

Primary laryngeal epithelial cells are essential to exploring the mechanisms of laryngeal and voice disorders; however, they are difficult to study and apply because of their limited life span. The purpose of this study was to develop a stable and reliable in vitro model for the comprehensive study of the pathogenesis of laryngeal and voice diseases. The pLVTHM-Bmi1 plasmid was constructed and used to immortalize primary laryngeal epithelial cells by lentiviral infection. The expressions of Bmi1, human telomerase reverse transcriptase (hTERT), p53, and pRB pathway proteins were detected by western blotting. Functional characteristics of the immortalized cell lines were verified by cell senescence ß-galactosidase staining, 5-ethynyl-2'-deoxyuridine cell proliferation test, and flow cytometry. We successfully introduced Bmi into human subglottic (hSG) cells and human ventricle (hV) cells. Both the human immortalized subglottic Bmi1 (hSG-Bmi1) cell line and the human immortalized ventricle Bmi1 (hV-Bmi1) cell line maintained normal epithelial morphology and divided successfully after more than 20 culture passages. As Bmi1 was overexpressed in these cells, the expression of human telomerase reverse transcriptase (hTERT) and phosphorylated Rb increased while p16 and p21 decreased. Following Bmi1-mediated immortalization, cell senescence decreased significantly, and cell proliferation was accelerated. Tumor formation was not observed for hSG, hV, or hSG-Bmi1, and hV-Bmi1 cells in nude mice. hSG-Bmi1 cells dominated by stratified squamous epithelium and hV-Bmi1 cells dominated by columnar cells were established. The new cell lines lay a foundation for the study of the pathogenic mechanisms of laryngeal and voice diseases.

Guidelines for parenteral and enteral nutrition in geriatric patients in China.

Based on the expert consensus on parenteral and enteral nutrition support for geriatric patients in China in 2013, domestic multidisciplinary experts were gathered to summarize the new evidence in the field of elderly nutritional support at home and abroad. The 2013 consensus was comprehensively updated and upgraded to a guideline by referring to the World Health Organization (WHO) guidelines for the Grading of Recommendations Assessment, Development, and Evaluation system for grading evidence. These guidelines were divided into two parts: general conditions and common diseases. After discussion by all members of the academic group and consultation with relevant experts, 60 recommendations were ultimately established as standardized nutritional support in the field of geriatrics in China.

Z-palatopharyngoplasty combined with 70-degree endoscopy-assisted coblator partial medial glossectomy on severe obstructive sleep apnea.

Background: Patients with severe obstructive sleep apnea (OSA) require safe and effective surgical treatment. Objectives: To evaluate the effectiveness of combined Z-palatopharyngoplasty (ZPPP) and partial glossectomy via 70-degree endoscopy-assisted coblation (Eco-TBR) on severe OSA. Materials and methods: Twenty-two consecutive patients with severe OSA were enrolled between September 2014 and July 2016. The lingual artery was evaluated by contrasted computed tomography (CT). Drug-induced sleep endoscopy (DISE) was performed to determine the necessity of multilevel surgery. Combined ZPPP and Eco-TBR were performed. Polysomnographic parameters were collected pre-operatively and 6 months post-operatively. Results: No adverse events were observed postoperatively. The short-term ( < 12 months) rate of total surgical effectiveness was 63.6% (14/22), with Friedman classifications as follows: I (1/1), Friedman II (6/10) and Friedman III (7/11). There were no differences between Friedman classification groups. The differences in AHI, apnea index (AI), mean blood oxygen, and percentage of cumulative time with oxygen saturation < 90% (CT 90%) were different compared to preoperative levels. Tonsil size was also significantly larger in the multi-level surgery group (2.14 ± 1.03) compared with the control group (1.13 ± 0.64). Conclusions and significance: Combined ZPPP and Eco-TB is safe and effective, with good surgical effectiveness for the treatment of severe OSA patients.

Attitudes Toward Advance Directives Among Patients and Their Family Members in China.

OBJECTIVES: Chinese people are generally unfamiliar with the concept of advance care planning or advance directives (ACP/ADs), which raises dilemmas in life-support choice and can even affect clinical decision making. To understand and address the issues involved better, we investigated the awareness of ACP/ADs in China, as well as people's attitudes toward medical autonomy and end-of-life care. DESIGN: A multicenter cross-sectional survey, conducted from August 1 to December 31, 2016. SETTING: Twenty-five hospitals located in 15 different provinces throughout mainland China. PARTICIPANTS: Pairs of adult patients without dementia or malignancies, and a family member. MEASUREMENTS: Participants self-filled anonymous questionnaires, and the data collected were analyzed to relate patients' sociodemographic characteristics to their awareness of ACP/ADs and attitudes to health care autonomy and end-of-life care. RESULTS: Among 1084 patients who completed the questionnaire, 415 (38.3%) had heard about ACP/ADs. Having been informed about ACP/ADs, 995 (91.8%) were willing to find out their true health status and decide for themselves; 549 (50.6%) wanted to institute ACP/ADs. Regarding end-of-life care, 473 (43.6%) chose Do Not Resuscitate, and 435 (40.1%) wished to forgo life-support treatment if irreversibly moribund. Patients predominantly (481, 44.4%) chose general hospital as their preferred place to spend their last days of life; only 114 (10.5%) favored a special hospice facility. Patients' main concerns during end-of-life care were symptom control (35.1%), followed by functional maintenance and quality of life (29.8%), and prolonging life (18.9%). More highly educated patients had significantly greater awareness of ACP/ADs than less well educated ones (χ2 = 59.22, P < .001) and were more willing to find out the truth for themselves (χ2 = 58.30, P ≤ .001) and make medical decisions in advance (χ2 = 55.92, P < .001). Younger patients were also more willing than older ones to know the truth (χ2 = 38.23, P = .001) and make medical decisions in advance (χ2 = 18.42, P = .018), and were also more likely to wish to die at home (χ2 = 96.25, P < .001). Only 212 patients' family members (19.6%) wanted life-support treatment for themselves if irreversibly moribund, whereas 592 (54.6%) would want their relative to receive such procedures in the same circumstances; a similar discrepancy was evident for end-of-life invasive treatment (18.3% vs 42.7%). CONCLUSIONS: Awareness about ACP/ADs in China is still low. Providing culturally sensitive knowledge, education, and communication regarding ACP/ADs is a feasible first step to promoting this sociomedical practice.

Rutaecarpine ameliorates hyperlipidemia and hyperglycemia in fat-fed, streptozotocin-treated rats via regulating the IRS-1/PI3K/Akt and AMPK/ACC2 signaling pathways.

AIM: We have shown that rutaecarpine extracted from the dried fruit of Chinese herb Evodia rutaecarpa (Juss) Benth (Wu Zhu Yu) promotes glucose consumption and anti-inflammatory cytokine expression in insulin-resistant primary skeletal muscle cells. In this study we investigated whether rutaecarpine ameliorated the obesity profiles, lipid abnormality, glucose metabolism and insulin resistance in rat model of hyperlipidemia and hyperglycemia. METHODS: Rats fed on a high-fat diet for 8 weeks, followed by injection of streptozotocin (30 mg/kg, ip) to induce hyperlipidemia and hyperglycemia. One week after streptozotocin injection, the fat-fed, streptozotocin-treated rats were orally treated with rutaecarpine (25 mg·kg(-1)·d(-1)) or a positive control drug metformin (250 mg·kg(-1)·d(-1)) for 7 weeks. The body weight, visceral fat, blood lipid profiles and glucose levels, insulin sensitivity were measured. Serum levels of inflammatory cytokines were analyzed. IRS-1 and Akt/PKB phosphorylation, PI3K and NF-κB protein levels in liver tissues were assessed; pathological changes of livers and pancreases were examined. Glucose uptake and AMPK/ACC2 phosphorylation were studied in cultured rat skeletal muscle cells in vitro. RESULTS: Administration of rutaecarpine or metformin significantly decreased obesity, visceral fat accumulation, water consumption, and serum TC, TG and LDL-cholesterol levels in fat-fed, streptozotocin-treated rats. The two drugs also attenuated hyperglycemia and enhanced insulin sensitivity. Moreover, the two drugs significantly decreased NF-κB protein levels in liver tissues and plasma TNF-α, IL-6, CRP and MCP-1 levels, and ameliorated the pathological changes in livers and pancreases. In addition, the two drugs increased PI3K p85 subunit levels and Akt/PKB phosphorylation, but decreased IRS-1 phosphorylation in liver tissues. Treatment of cultured skeletal muscle cells with rutaecarpine (20-180 µmol/L) or metformin (20 µmol/L) promoted the phosphorylation of AMPK and ACC2, and increased glucose uptake. CONCLUSION: Rutaecarpine ameliorates hyperlipidemia and hyperglycemia in fat-fed, streptozotocin-treated rats via regulating IRS-1/PI3K/Akt signaling pathway in liver and AMPK/ACC2 signaling pathway in skeletal muscles.

Proteomic identification of alpha-2-HS-glycoprotein as a plasma biomarker of hypopharyngeal squamous cell carcinoma.

Hypopharyngeal squamous cell carcinoma (HSCC) has very poor prognosis compared with other head and neck squamous cell carcinomas. Late-stage diagnosis of HSCC increases mortality. Therefore, more effective biomarkers for early diagnosis of HSCC are necessary. Unfortunately, appropriate biomarkers for clinical diagnosis and prognosis have not been identified yet. However, recent progresses in quantitative proteomics have offered opportunities to identify plasma proteins as biomarkers for HSCC. In the present study, plasma samples were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE), and differentially expressed proteins were identified by matrix assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). A total of 26 proteins representing 12 unique gene products were identified. The up-regulation proteins were alpha-2-HS-glycoprotein (AHSG), complement C4-B, haptoglobin, C-reactive protein, and ceruloplasmin, whereas the down-regulation proteins were serum albumin, angiotensinogen, alpha-1-antichymotrypsin, Ig gamma-3 chain C region, fibrinogen gamma chain, apolipoprotein A-I, and Ig kappa chain C region. Among all the differentially expressed proteins, AHSG was validated by western blot and ELISA. The results were consistent with the data from 2D-DIGE, further suggesting that AHSG may be employed as a potential biomarker for the early diagnosis of HSCC. In summary, this study was the first to use 2D-DIGE and MALDI-TOF/TOF platform to identify the potential plasma biomarkers for HSCC. The plasma AHSG showed great potential for HSCC screening.

Guidelines for parenteral and enteral nutrition support in geriatric patients in China.

The mortality and morbidity of geriatric patients is much higher than for younger patients, especially when critically ill. This may be attributed to a lower reserve capacity in most organs and systems, reduced ability to deal with physical stress and the presence of acute or chronic co-mobidities. Parenteral and enteral nutrition support can improve the clinical condition of the elderly patient and result in better outcomes, such as lower mortality, reduced hospital stay and reduced medical costs. There is a need to standardize nutrition screening and assessment, and the implementation of appropriate evidence based nutritional support of geriatric patients in China. The Chinese Medical Association's Group of Geriatric Nutrition Support has developed guidelines by researching the present situation in Chinese hospitals and by referring to the guidelines from both American Society for Parenteral and Enteral Nutrition (ASPEN) and the European Society for Clinical Nutrition and Metabolism (ESPEN).

[A preliminary study on the assessment of swallowing function after supracricoid partial laryngectomy].

OBJECTIVE: To investigate a reliable and easy assessment method for swallowing function by evaluating objectively the recovery process of swallowing function in patients six months after supracricoid partial laryngectomy. METHODS: The swallowing function of patients who underwent supracricoid partial laryngectomy was evaluated six months after operation in Nanfang Hospital of Southern Medical University between January 2013 and February 2014 with two methods, the modified barium swallow (MBS) and fiberoptic endoscopic evaluation of swallowing (FEES), combined with modified penetration aspiration scale (MPAS). Furthermore, the feasibility, reliability and accuracy of these two methods were compared. RESULTS: Eleven patients were enrolled. MPAS equals score 1 for solid food, semiliquid food, and liquid food was defined as a criteria of normal swallowing function. By MBS evaluation, the numbers of patients with normal swallowing function were two cases at day 16-30 postoperation, two cases at day 31-45 postoperation, five cases at day 46-90 postoperation, and six cases at day 91-180 postoperation, respectively. By FEES evaluation, the above numbers were three cases, four cases, six cases and eight cases, respectively. When the aspiration was minimal and ejected completely and MPAS was less than or equal to score 4 for solid food, semiliquid food, and liquid food, the gastric tube could be removed. According to this standard, the gastric tube was removed in all cases, and the mean time was (21.7 ± 9.8) days. A good correlation was obtained between these two methods when evaluating solid and semiliquid food, and the Kappa values were 0.802 and 0.844, respectively. However, a little agreement was obtained between these two methods when evaluating liquid food, and the Kappa value was 0.529. CONCLUSIONS: Patients who underwent supracricoid partial laryngectomy could restore good swallowing function in six months after the operation. Both the MBS and FEES are valuable procedures for evaluating objectively the swallowing function in patients after supracricoid partial laryngectomy. The FEES is much better than MBS, because FEES is a simple operation performed alone by otolaryngologists with no radiation.

Umbilical cord-derived mesenchymal stem cell therapy for neurological disorders via inhibition of mitogen-activated protein kinase pathway-mediated apoptosis.

The present study investigated the recovery and intrathecal administration of human umbilical cord­derived mesenchymal stem cells (HUC­MSCs) by lumbar puncture and analyzed the technical difficulties and short and long­term effects of UC­MSC transplantation in various neurological conditions. In total, 100 patients who underwent subarachnoid placement of UC­MSCs between December 2006 and May 2010 were included in the present study. The present study evaluated the number of attempts, localization of subarachnoid space and postprocedural complications. The Hauser Ambulation Index was employed for functional assessment. Clinical symptoms, the associated biochemical index and photographic examinations were observed regularly. HUC­MSCs were transplanted into mice as well as patients in order to determine the underlying therapeutic mechanisms. Technical difficulties were encountered in 31 patients (31%) in the form of general anesthesia supplementation and difficulty localizing lumbar space. Side effects were observed in 22 (22%) patients, which resolved with symptomatic treatment within 48 h. On follow­up one year later, functional indices improved in 47 (47%) patients. Transplantation of HUC­MSCs inhibited apoptosis and the protein expression of c-Jun N-terminal kinase and p38 as well as triggered the phosphorylation of P­42/44 extracellular-signal-regulated kinase. In conclusion, intrathecal administration of UC­MSCs is safe and effective with no long­term adverse effects in neurological disorders. HUC­MSCs may achieve these effects via the mitogen­activated protein kinase pathway. The results suggest that there is a promise of restoration of lost tissue and improvement of function in patients with profound neurological defects. These data support expanded double blind, placebo­controlled studies for this treatment modality.

[Multiple factors quantitative analysis on middle ear function in primarily diagnosed patients with nasopharyngeal carcinoma].

OBJECTIVE: To explore the ways of quantitative and objective evaluation for analyzing the multiple influence factors on middle ear function in the patients with primarily diagnosed NPC, and to analyze the influence factors of middle ear function in the patients with primarily diagnosed nasopharyngeal carcinoma (NPC). METHOD: Three hundred and twenty cases (320 ears) of primarily diagnosed NPC patients were examinated with electric otoscope, acoustic immittance measurement, pure tone audiometry, nasopharynx and middle ear CT or MRI scanning, eustachian tube function examination, and electronic nasopharyngoscope. A series of quantitative methods, as the influence factors including T stage, clinical stage, location, diffusion type and form of tumor, eustachian tube function, pharynx mouth shape, imaging extension (nasal, skull base, pharyngeal recess, parapharyngeal space, tensor veli palatini muscle, levator veli palatini and so on), were used to evaluate the middle ear function. SPSS 13.0 was used to anlyze the single and multiple factors in statistics. RESULT: T stage, clinical stage, location, diffusion type, and form of tumor, pharynx mouth shape, imaging extension (nasal, skull base, pharyngeal recess, parapharyngeal space, tensor veli palatini muscle, levator veli palatini) were the single influence factors on the function of middle ear in primarily diagnosed NPC patients. The gender, age, pathological types, N staging and M staging of NPC patients primarily diagnosed had no effect on middle ear function. The multple factors analysis showed that T stage, tumor location, the function of eustachian tube, tensor veli palatini muscle invasion, and skull base invasion were independent factor of affecting the middle ear function on primarily diagnosed NPC patients. CONCLUSION: In this study, the influence factors of middle ear function with primarily diagnosed NPC were related to T stage, location of tumor, the function of eustachian tube, tensor veli palatini muscle invasion, skull base invasion, otitis media and quantitative criteria. The way of quantitative analysis could be used to evaluate objectively the middle ear function in patients with primarily diagnosed NPC.

Levels of brain natriuretic peptide are associated with peripheral arterial disease in subjects with type-2 diabetes mellitus.

BACKGROUND: The effects of brain natriuretic peptide (BNP) on the risk of cardiovascular disease and atherosclerosis have been studied. However, little information is available regarding peripheral arterial disease (PAD), particularly among subjects with type-2 diabetes mellitus (T2DM). The aim of our study was to assess the potential relationship between BNP levels and PAD among T2DM patients. METHODS: The study cohort was 507 T2DM outpatients in which BNP levels were measured. Cross-sectional associations between BNP levels (in tertiles) and PAD were examined. RESULTS: Compared withT2DM patients without PAD, BNP levels were markedly higher in patients with PAD (p = 0.001). Correlation analyses showed that the BNP level was negatively correlated with the ankle-brachial index (r = -0.453, p = 0.033). At a cutoff value of 78.2 pg/ml, the BNP level showed a sensitivity of 71.9%, a specificity of 68.1%, and a positive predictive value of 84.3% for a diagnosis of PAD. The area under the receiver-operating characteristic curve increased significantly if BNP levels were incorporated into a predictive model of the potential risk factors for PAD (0.85 vs 0.81, p = 0.029). CONCLUSIONS: BNP is a potential and promising biomarker for PAD screening in T2DM patients.

MicroRNA-378 functions as an onco-miR in nasopharyngeal carcinoma by repressing TOB2 expression.

Increasing evidence indicates that microRNAs (miRNAs) has been implicated in the progression and metastasis of numerous cancers. In particular, abnormal expression of miR-378 has been observed in various cancers and is associated with cell survival, migration, invasion, angio-genesis and tumor growth. Our previous studies have shown that miR-378 was decreased in nasopharyngeal carcinoma (NPC) plasma and was negatively correlated with NPC progression. However, the tissue expression of miR-378 and its biological function remained unknown in NPC. In this study, we report for the first time that expression level of miR-378 was commonly upregulated in both NPC tissues and NPC cell lines compared to normal healthy nasopharyngeal epithelial samples and human nasopharyngeal epithelial cell lines (NP69), respectively, and was opposite to the reported results in plasma. Functional studies showed that upregulation of miR-378 dramatically promoted cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth in vivo. Bioinformatics analyses were performed to predict the target genes of miR-378, and the following mechanistic investigations revealed that miR-378 overexpression was able to downregulate the expression of transducer of ERBB2 (TOB2), a potential tumor suppressor, and miR-378 silencing enhanced TOB2 expression. In clinical specimens, TOB2 was widely repressed in tumor tissues accompanied by miR-378 overexpression. Taken together, this study indicates that miR-378 regulates TOB2 and may function as an onco-miR in NPC progression, providing a potential target for gene therapy of NPC.

Positivity of both plasma Epstein-Barr virus DNA and serum Epstein-Barr virus capsid specific immunoglobulin A is a better prognostic biomarker for nasopharyngeal carcinoma.

BACKGROUND: Positivity of plasma Epstein-Barr virus (EBV)-DNA or serum virus capsid antigen-specific IgA (VCA-IgA) is a biomarker for the prognosis of nasopharyngeal carcinoma (NPC). The objective of this study was to determine the value of positivity for plasma EBV-DNA and/or VCA-IgA in predicting the survival of patients with NPC. METHODS: Plasma EBV-DNA and serum VCA-IgA in 506 NPC patients in this retrospective study were detected by quantitative real time polymerase chain reaction and enzyme-linked immunoabsorbent assay, respectively. The value of positivity for EBV-DNA and/or VCA-IgA in predicting the survival of patients with NPC was analyzed. RESULTS: Patients with positivity for both EBV-DNA and VCA-IgA had significantly shorter periods of relapse free survival (RFS) and overall survival (OS) than those with positive single measure or negative for both measures, and patients with positive single measure had significantly shorter periods of RFS and OS than those with negative for both. Multivariate analysis indicated that the positivity for EBV-DNA and/or VCA-IgA were significant risk factors for shorter periods of RFS and OS. CONCLUSION: These data indicated that positivity for both EBV-DNA and VCA-IgA was a better biomarker for the prognosis of patients with NPC. Our findings may provide new references for clinical practice.