Currently hypoglossal nerve–genioglossus axis is the major research core of OSA pathogenesis. The pathogenesis of OSA incidence changes before and after menopause needs to be clarified further. Little is known about the influences of ovariectomy on hypoglossal motoneurons. In the research, we utilized a rat ovariectomy model to evaluate the expression changes of 5-HT2A and α1-Adrenergic receptors in the hypoglossal nucleus and to explore the involvement of BDNF/TrkB signaling and endoplasmic reticulum molecular chaperones in the hypoglossal nucleus. Results indicated that the expression of 5-HT2A and α1-Adrenergic receptors reduced dramatically in the hypoglossal nucleus of ovariectomized rats. The apoptosis level of hypoglossal motor neurons increased markedly in the OVX groups. The up-regulated expression of BDNF and down-regulated expression of TrkB were found in the OVX groups. Ovarian insufficiency resulted in the activation of UPR and the loss of CANX-CALR cycle. Estrogen replacement could restore these changes partially. Estrogen level influences the expression of neurotransmitter receptors, and regulates BDNF/TrkB signaling compensation and endoplasmic reticulum homeostasis, which might be one of the pathogenesis of menopausal female OSA. The results reveal a new perspective for studying female OSA from the view of hypoglossal nerve and hormonal changes and attempt to propel 17β-estradiol toward a feasible therapy for female OSA.

Objective: Inferior vena cava (IVC) filters are often used. However, no clear consensus has been reached regarding the benefits and risks from randomized, controlled trials. Therefore, we investigated benefits and risks of IVC filter use. Methods: The PubMed and Cochrane Library databases were searched from inception to October 31, 2019 to identify randomized, controlled trials for inclusion in our meta-analysis. The primary outcome was mortality related to pulmonary embolism (PE). The secondary outcomes were overall mortality, PE, deep vein thrombosis, and major bleeding. Risk ratios were pooled using the Mantel-Haenszel method with the fixed effects model for low heterogeneity. Otherwise, the random effects model was used. Risk differences were considered candidates of effect size if some of the data could not be pooled in the calculations. Results: Seven articles with 1274 patients were included. We found no significant difference in mortality related to PE between the IVC filter and control groups within 3 months (risk difference, -0.01; 95% confidence interval, -0.03 to 0.00; P = .11) nor during the entire follow-up period with low heterogeneity (I-2 = 0%). The new occurrence of PE within 3 months and during the whole follow-up period was lower in the IVC filter group than in the control group (0.81% vs 5.98%; risk ratio, 0.17; 95% CI, 0.04-0.65; P = .01; and 3.2% vs 7.79%; risk ratio, 0.42; 95% CI, 0.25-0.71; P = .001, respectively). No significant differences were found in the rates of the new occurrence of deep vein thrombosis, major bleeding, and mortality during the whole follow-up period between the two groups (P > .05). Conclusions: We found insufficient evidence to conclude that the use of IVC filters can reduce mortality. However, the use of IVC filters decreased the new occurrence of PE without increasing deep vein thrombosis or major bleeding.

IntroductionPatients with cancer are more vulnerable to COVID-19 than the general population. Accordingly, it is necessary to identify the risk factors for death in patients with cancer and COVID-19.MethodsPubMed, Cochrane Library, and Embase Ovid databases were searched for relevant articles published before July 31(st), 2020. Studies that explored the risk factors for mortality were included. The effect size was relative risk (RR) and 95% confidence interval (CI).ResultsWe included 17 observational studies involving 3268 patients. The pooled mortality was 24.8%. Male gender, age above 65 years, and comorbidities (especially hypertension and COPD) were risk factors for death (RR 1.16, 1.27, 1.12; 95% CI 0.7-1.95, 1.08-1.49, 1.04-1.2; P = 0.006, 0.004, and 0.002, respectively). Recent anti-cancer treatments did not increase mortality (P 0.05). Dyspnea, cough, and sputum canused an elevated risk of death (P 0.05). Antibiotics, glucocorticoids, interferons, invasive ventilation, and complications were associated with a high probability of death (P 0.05).ConclusionsVarious demographic and clinical characteristics, such as male gender, advanced age, comorbidities, and symptoms, were risk factors for mortality in patients with cancer and COVID-19. Our findings suggest recent anti-cancer treatments do not increase mortality.

Objective To investigate the predictive value of extra pulmonary multiple factors including creatine kinase-isoenzyme MB (CK-MB) for the prognosis of patients with acute paraquat poisoning.Methods A retrospectively analysis were conducted on 641 patients who were treated at the First Affiliated Hospital of Zhengzhou University due to oral paraquat poisoning from October 2002 to April 2017.The observation end point was that the patients died from paraquat poisoning within 3 months after admission or were still alive within 3 months after paraquat poisoning.The patients' data were retrieved,including general information,the dose of poison,urinary paraquat concentration,arterial blood gas analysis,alanine transaminase (ALT),total bilirubin (TBIL),uric acid (UA),aspartate transaminase (AST),creatine kinase (CK),CK-MB,B type natriuretic peptide (BNP),lactic dehydrogenase (LDH),high sensitivity troponin T (hsTnT),C-reaction protein (CRP) and procaicitonin (PCT).According to the patient's prognosis within 3 months,the patients were divided into a survival group and a non-survival group.The above indicators were compared between the two groups and the diagnostic value of CK-MB for acute paraquat poisoning was analyzed according to the receiver operating characteristics (ROC) curve.Collect the last arterial blood gas analysis,and laboratory test results were analyzed by binary logistic regression analysis to determine the risk factors for death in patients with acute paraquat poisoning.Results Among the 641 patients with acute paraquat poisoning,315 (49.1％) patients survived and 326 (50.9％) died.Compared with the survival group,patients in the non-survival groupthere were older,had a shorter hospital stay,and had a higher oral paraquat dose and urinary paraquat concentration;Lac,TBIL,UA,AST,CK,CK-MB,BNP,LDH,CRP and PCT were higher,while blood gas analysis index were lower in the non-survival group (P＜0.05).Binary logistic regression analysis showed that the dose of paraquat,CK-MB and AST were closely related to the prognosis of patients with acute paraquat poisoning.The optimal cut-off value of ingestion dose,the first urinary paraquat concentration on admission and CK-MB in predicting the prognosis of patients with acute paraquat poisoning were 7 g (AUC=0.918,sensitivity 80.6％,specificity 87.5％,Yoden index 0.681,P＜0.01),5.16 μg/mL (AUC=0.879,sensitivity 93.8％,specificity 70.1％,Yoden index 0.639,P＜0.01),and 18.2 U/L (AUC=0.846,sensitivity 83.9％,specificity 71.9％,Yoden index 0.558,P＜0.01),respectively.Binary logistic regression analysis of the last biochemical indicators of paraquat poisoning showed that the dose of poison,the last CK-MB,the last SCr,urinary paraquat concentration,and the last blood Na+ were closely related to the prognosis of patients with acute paraquat poisoning.Among them,the last CK-MB＞18.05 U/L often indicated poor prognosis (AUC=0.808,sensitivity 79.7％,specificity 65.8％,Yoden index 0.455,P＜0.01).Conclusions In the treatment of patients with acute paraquat poisoning,there are significant differences in extra pulmonary factors such as heart,liver,kidney,electrolytes and inflammatory markers in patients with different prognosis,so the monitoring and follow-up should be improved,in addition to focusing on the presence and treatment of pulmonary fibrosis.In particular,CK-MB is an independent risk factor for the prognosis of acute paraquat poisoning.In the late stage of poisoning,CK-MB,SCr,and blood Na+ have a strong predictive value for the prognosis of the patients,and we should pay attention to the regular follow-up of the above mentioned laboratory items.

目的 探讨肝损伤指标对急性百草枯中毒患者预后的评估价值.方法 回顾性分析2013年3月至2017年4月郑州大学第一附属医院急诊科收治的479例急性百草枯中毒患者的临床资料,按中毒后30 d内预后分为存活组(284例)和病死组(195例).采用多因素Logistic回归分析百草枯中毒死亡的独立危险因素,并绘制受试者工作特征(ROC)曲线评价相关因素的预测效果.结果 多因素Logistic回归分析显示,服毒量、尿百草枯水平、直接胆红素、AST、ALT是急性百草枯中毒死亡的独立危险因素(均P<0.05).ROC曲线显示,服毒量、尿百草枯水平、直接胆红素、AST、ALT预测急性百草枯中毒患者预后的ROC曲线下面积(AUC)分别为0.898、0.891、0.674、0.790、0.709.服毒量30 mL为判断预后的临界值(灵敏度85.57％,特异度79.23％),尿百草枯水平临界值为12.67μg·mL-1(灵敏度84.02％,特异度78.37％),直接胆红素临界值为8.2μmol·L-1(灵敏度38.46％,特异度92.23％),AST临界值为36 U·L-1(灵敏度50.77％,特异度93.31％),ALT临界值为17 U·L-1(灵敏度68.72％,特异度64.08％).结论 除服毒量、尿百草枯水平外,肝功能指标中直接胆红素、AST及ALT也是百草枯中毒预后较简单可靠的预测因子.

Objective To investigate the evaluation value of white blood cell count ( WBC ) for the prognosis of patients with acute paraquat ( PQ) poisoning .Methods The clinical data of 661 patients with acute PQ poisoning admitted to the Emergency Department of the First Affiliated Hospital of Zhengzhou University from March 2013 to April 2017 were retrospectively analyzed . The general information of patients and biochemical indicators 24 hours after admission were collected .The in-hospital death were recorded and patients were followed up by telephone .According to the prognosis within 30 days after poisoning , the patients were divided into survival group and death group .Multivariate logistic regression analysis was used to analyze the independent risk factors of PQ poisoning , and the receiver operating characteristic curve ( ROC ) was drawn for prognosis evaluation .Results Among the 661 patients with acute PQ poisoning , 368 cases ( 55.7％) survived and 293 cases ( 44.3％) died. Multivariate logistic regression analysis showed that hospitalization days , dosage , duration of poisoning , urine PQ concentration, WBC, serum potassium and serum creatinine (Scr) were the independent risk factors.The ROC curve showed that the area under the ROC curve (AUC) of urine PQ concentration and WBC predicting the prognosis of patients with acute PQ poisoning were 0.897 [95％CI(0.873, 0.920), P<0.01], and 0.876 [95％CI(0.850, 0.902), P<0.01].WBC≥15.35 ×109/L was used as the critical value for prognosis . The sensitivity and specificity of survival were 72.7％ and 88.59％, respectively .Conclusions White blood cell count may be a powerful and simple predictor for prognosis of PQ.

Acute severe ammonia inhalation can seriously affect oxygenation and ventilation function of patients, and even cause acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) technology is increasingly used in treating patients with ARDS caused by infection, cardiogenic shock, trauma, and drowning with achieved certain effects, but its usage for ARDS caused by ammonia is rarely reported. On July 7, 2018, a case of ARDS caused by ammonia inhalation was admitted to the emergency ICU of the First Affiliated Hospital of Zhengzhou University. After admission, the patient was treated with ECMO immediately on the basis of anti-infection, anti-oxidation, suctioning and nebulization treatments. After 8 days, he was weaned from ECMO and transferred to a general ward for continued rehabilitation. After 23 days, his condition improved and was discharged without complaining of any discomfort during the follow-up till March 2019. The successful experience was summarized in order to provide reference for the treatment of such patients in the future.

The integrity of the endothelial barrier is a determinant of the prognosis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). In this study, we investigated whether and how Sirtuin 1 (SIRT1) maintained the vascular integrity during ALI. An experimental model of ALI was established in mice through intratracheal administration of LPS (10 mg/kg). LPS stimulation significantly increased the pulmonary permeability and decreased the expression of SIRT1 and tight junction proteins (TJs), including occludin, claudin-5, tight junction protein 1 and tight junction protein 2. Morphological studies showed that LPS induced obvious lung injury with inflammatory cell infiltration in the interstitial and alveolar space, hemorrhage, edema, and the thickened alveolar wall compared to the control mice. Intratracheal administration of the selective SIRT1 activator SRT1720 (6.25 mg/kg) significantly attenuated LPS-induced lung injury, lung hyper-permeability and increased TJs expression, whereas intratracheal administration of the selective SIRT1 inhibitor EX527 (6.25 mg/kg) aggravated LPS-induced ALI. Similar protective effects of SIRT1 on pulmonary cellular permeability were observed in primary human pulmonary microvascular endothelial cells treated with LPS (2 mg/mL) in vitro. We further demonstrated that the RhoA/ROCK signaling pathway was activated in SIRT1 regulation of tight junction permeability. The RhoA/ROCK inhibitor Y-27632 (10 μM) increased the expression of TJs and reversed LPS- or EX527-induced hyper-permeability. In conclusion, SIRT1 ameliorates LPS-induced lung injury via decreasing endothelial tight junction permeability, possibly via RhoA/ROCK signaling pathway. This finding may contribute to the development of new therapeutic approaches for lung injury.

Pulmonary hypertension (PH) is prevalent in patients with obstructive sleep apnea (OSA) syndrome, and coexistence of PH and OSA indicates a worse prognosis and higher mortality. Chronic intermittent hypoxia (CIH) is the key pathogenesis of OSA. Also, microRNA‐223 (miR‐223) plays a role in the regulation of CIH‐induced PH process. However, the detailed mechanism of CIH inducing PH is still unclear. This study aimed to investigate the pathological process of CIH associated PH and explore the potential therapeutic methods. In this study, adult Sprague–Dawley rats were exposed to CIH or normoxic (N) conditions with 2‐methoxyestradiol (2‐Me) or vehicle treatment for 6 weeks. The results showed that 2‐Me treatment reduced the progression of pulmonary angiogenesis in CIH rats, and alleviated proliferation, cellular migration, and reactive oxygen species formation was induced by CIH in pulmonary artery smooth muscle cells (PASMCs). CIH decreased the expression of miR‐223, whereas 2‐Me reversed the downregulation of miR‐223 both in vivo and in vitro. Furthermore, the antiangiogenic effect of 2‐Me observed in PASMCs was abrogated by miR‐223 inhibitor, while enhanced by miR‐223 mimic. These findings suggested that miR‐223 played an important role in the process of CIH inducing PH, and 2‐Me might reverse CIH‐induced PH via upregulating miR‐223.

Objective:To evaluate the effect of continuous positive airway pressure (CPAP) on symptoms and the quality of life of patients with mild obstructive sleep apnea hypopnea syndrome (OSAHS) complicated with somnolence.Methods:Seventy-four patients with mild OSAHS were recruited.Epworth sleepiness scale (ESS) was used to evaluate the degree of somnolence.Patients with ESS scores more than ten were designated as somnolence,and CPAP was conducted.Patients with ESS scores less than ten were designated as non-somnolence,and health education was conducted.Quebec sleep questionnaire (QSQ) was adopted to evaluate the quality of life.All patients were followed up for eight weeks.Results:After CPAP treatment,the ESS scores of mild OSAHS patients significantly decreased (P＜0.01),and the QSQ scores significantly increased (P＜0.01),indicating that CPAP treatment can improve the somnolence and quality of life in patients with mild OSAHS.Conclusions:Patients with mild OSAHS have different degrees of somnolence,which leads to a decline in quality of life.CPAP can improve somnolence and quality of life in patients with mild OSAHS.

Evidence has shown that hypoxic episodes elicit hypoglossal neuroplasticity which depends on elevated serotonin (5-HT), in contrast to the rationale of obstructive sleep apnea (OSA) that deficient serotonergic input to HMs fails to keep airway patency. Therefore, understanding of the 5-HT dynamic changes at hypoglossal nucleus (HN) during chronic intermittent hypoxia (CIH) will be essential to central pathogenic mechanism and pharmacological therapy of OSA. Moreover, the effect of CIH on BDNF-TrkB signaling proteins was quantified in an attempt to elucidate cellular cascades/synaptic mechanisms following 5-HT alteration. Male rats were randomly exposed to normal air (control), intermittent hypoxia of 3 weeks (IH3) and 5 weeks (IH5) groups. Through electrical stimulation of dorsal raphe nuclei (DRN), we conducted amperometric technique with carbon fiber electrode in vivo to measure the real time release of 5-HT at XII nucleus. 5-HT2A receptors immunostaining measured by intensity and c-Fos quantified visually were both determined by immunohistochemistry. CIH significantly reduced endogenous serotonergic inputs from DRN to XII nucleus, shown as decreased peak value of 5-HT signals both in IH3 and IH5groups, whereas time to peak and half-life period of 5-HT were unaffected. Neither 5-HT2A receptors nor c-Fos expression in HN were significantly altered by CIH. Except for marked increase in phosphorylation of ERK in IH5 rats, BDNF-TrkB signaling and synaptophys consistently demonstrated downregulated levels. These results suggest that the deficiency of 5-HT and BDNF-dependent synaptic proteins in our CIH protocol contribute to the decompensated mechanism of OSA.

BACKGROUND Obstructive sleep apnea-hypopnea syndrome (OSAHS) could cause systematic inflammation including pulmonary inflammatory response, whereas the influence of OSAHS in pulmonary clearance ability remains unknown. The main pathophysiological feature of OSAHS is chronic intermittent hypoxia (CIH). The goal of this study is to clarify the airway clearance of particulate matter (PM) in CIH mice, and to explore the potential mechanism. METHODS Balb/c mice were divided into a CIH group and a control group, exposed to intermittent hypoxia and air chamber, respectively. A radioactive probe, 99mTc labeled PM, was endotracheally inserted into the mice at 10 mg/kg, with a starting dose of 800 μCi. The change of radioactive dose reserved in the lung was observed using single-photon emission computed tomography/computed tomography (SPECT/CT) and reconstructed data were analyzed. Special airway resistance (sRaw) of mice was measured by non-invasive airway mechanics sites. Lung resistive load (RL), elastic resistance, and compliance were measured by a multichannel physiological signal system. Lung injury was judged by hematoxylin-eosin staining and histologic score. Change in mucus secretion was determined using periodic acid-Schiff staining and enzyme-linked immunosorbent assay. Fresh lung tissue was used for real-time polymerase chain reaction and western blot analysis to explore related change of inflammation and signaling molecules and potential mechanical pathway. RESULTS Mice in the CIH group had higher PM radioactive deposit than the control group (93.37±3.44 μCi vs. 65.98±2.61 μCi). The average radiation dose in the lung was elevated (0.0005 μCi/mm3 vs. 0.0001383 μCi/mm3). Mice in the CIH group have higher value of sRaw, RL, and elastic resistance, whereas pulmonary compliance decreased compared to the control group (2.13±0.29 mL/cmH2O vs. 5.37±1.02 mL/cmH2O). The CIH group showed a higher histopathological score. Several genes associated with mucin secretion such as chemokine (C-X-C motif) ligand 1 (CXCL1), Clara Cell Secretory Protein 16 (CC16), macrophage inflammatory protein 2 (MIP-2), chloride channel regulator 1 (Gob5), and mucin 5AC (MUC5AC) showed elevated expression. Phosphatidylinostol-3-kinase/serine/threonine-specific protein kinase (PI3K/AKT) pathway was activated in the CIH group. CONCLUSIONS CIH decreased pulmonary clearance of PM and increased lung airway resistance, which may be related to inflammatory response and mucus hypersecretion in the lung.

BACKGROUND The bidirectional relationship of asthma and obstructive sleep apnea (OSA) has been confirmed in recent years. However, in the clinical practice, majority of asthma patients did not pay adequate attention to their sleep apnea condition. Berlin questionnaire (BQ) and STOP-Bang questionnaire (SBQ) are two most common OSA screening questionnaires to screen high-risk patients for OSA. This study aimed at evaluating the predictive performance of BQ and SBQ for OSA in asthma patients. METHODS Asthma outpatients of Zhongshan Hospital were enrolled into the study. All patients were asked to fill in the BQ and SBQ and clinical characteristics and asthma characteristics were recorded. Univariate and multivariate logistic regression analyses were applied to identify risk factors of OSA in asthma patients. With the gold standard of laboratory-based overnight polysomnography (PSG), the predictive performance of SBQ and BQ was evaluated and compared. The probability of OSA severity was predicted by various SBQ scores in asthma patients. RESULTS A total of 123 asthma patients (average age 47.56±12.12 years; 57.72% males) were enrolled and underwent PSG diagnosis overnight at Sleep Center. Logistic regression analyses showed that rhinitis (adjusted OR =4.30; 95% CI: 1.50-12.37, P=0.007) and dyslipidemia (adjusted OR =2.75; 95% CI: 1.16-6.51, P=0.021) were associated with OSA in asthma patients after adjusting for known OSA risk factors. No asthma functional characteristic differences were found to be associated with OSA severity in the study. The prevalence of moderate-to-severe OSA (AHI ≥15) in the asthmatic population sample was 36.59% (45/123). Questionnaires predictive results showed that compared with BQ, SBQ has higher diagnostic sensitivity (84.4% vs. 60%), lower specificity (79.5% vs. 91%) lower positive predictive value (PPV): (70.4% vs. 79.4%) and higher negative predictive value (NPV) (90% vs. 80%) to detect moderate-to-severe OSA at the cut-off as AHI of 15/h. OSA probability results showed that with the increasing of the questionnaire scores, the moderate and severe OSA probability of SBQ rose significantly. CONCLUSIONS SBQ is a preferable sleep questionnaire better than BQ for detecting moderate and severe OSA in asthma patients which should be validated in larger population sample.

The aim of the present study was to investigate the effects of transketolase (TKT) on cell proliferation, cell migration and interaction with other metabolism-associated genes in A549 lung cancer cells. A549 cells were transfected with three TKT-specific small interfering (si)RNAs, screened for the optimal transfection concentration, and sequenced with flow cytometry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell viability was evaluated using Cell Counting Kit-8 (CCK-8), cell cycle was assessed by flow cytometric analysis. Cell migration was determined by scratch-wound and Transwell chamber assays. The changes in mRNA expression levels of glucose-6-phosphate dehydrogenase (G6PDH), transaldolase (TAL), sorbitol dehydrogenase (SORD), phosphoribosyl pyrophosphate synthetase 1 (PRPS1) and hexokinase 1 (HK1) were detected by RT-qPCR. siRNA-C at 50 nmol/l was selected for the subsequent experiments. Compared with the negative control, cell proliferation of the TKT-siRNA-C group was inhibited dramatically (CCK-8 24 h, 0.2984±0.0371 vs. 0.0952±0.0063; P<0.0001), the cell cycle was arrested at the G1/G0 cell cycle phase (58±2.0% vs. 70±2.5%; P=0.002), and cell migration ability was decreased [wound size, 254.71±34.96 vs. 349.12±37.43 µm (P=0.0001); Transwell migration, 250±47.8/field vs. 150±49.0/field (P<0.0001)]. The mRNA expression levels of G6PDH, TAL, SORD, PRPS1 and HK1 were downregulated in the TKT-siRNA-C group compared with the negative control. The present study revealed that synthetic TKT-siRNA can inhibit A549 cell viability and migration, which may be due to arrest of the cell cycle and downregulation of relevant metabolic enzymes.

Chronic intermittent hypoxia is the primary pathophsiological feature of obstructive sleep apnea/hypopnea syndrome. The characteristics of CIH can be imitated by animal experiment models thus to study CIH related systemic organ injuries, including respiratory systems.

Obstructive sleep apnea (OSA) associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered tissue damage. Receptor for advanced glycation end product (RAGE) and its ligand high mobility group box 1 (HMGB1) are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE), the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1) normal air (NA), (2) CIH, (3) CIH+sRAGE, and (4) NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6), apoptotic (Bcl-2/Bax), and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK) signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

SESSION TITLE: Lung Cancer II SESSION TYPE: Original Investigation Poster PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM PURPOSE: To study the effect of cell proliferation and apoptosis in A549 lung cancer cells and to find out the influence on other key enzymes of metabolism. METHODS: With three chemosynthesis siRNA Duplex targeting transketolase (TKT), A549 lung cancer cells were cultured and transfected. One of the best siRNA with highest interference effect was selected by fluorogenic Quantitative PCR. Transfection cells of 48h and 72h were detected by Flow Cytometry for cell cycle and apoptosis and by fluorogenic Quantitative PCR to record the changes of other metabolic key enzymes mRNA. RESULTS: The results showed that after transfection 48h the proportion of G1/G0 cells in Mock group and siRNA group were respectively and the proportion of G2/M+S cells in Mock group and siRNA group were respectively, no significant difference was found; After transfection 72h the proportion of G1/G0 cells in Mock group and siRNA group were respectively, the difference was statistically significant, and the proportion of G2/M+S cells in Mock group and siRNA group were respectively, the difference was statistically significant, P=0.002. Quantitative PCR results showed that after transfection 48h the relative expression of TKT mRNA decreased significantly while the relative expression of G6PDH, TAL and SORD mRNA didn't change significantly; transfection 72h the relative expression of TKT mRNA decreased significantly and the relative expression of G6PDH, TAL, PRPS1, HK1 and SORD mRNA decreased significantly, the relative expression of HK2 mRNA didn't change significantly. CONCLUSIONS: Quantitative PCR results showed that the best interference effect was found in siRNA-A group (Negative control: siRNA groups ratio is 1: 0.35). TKT mRNA interference inhibit A549 cell proliferation, the proportion of G2/M+S cells decreases and cell cycle arrest in the G1/G0 stage. CLINICAL IMPLICATIONS: TKT mRNA interference has a great influence on the normal metabolism and proliferation of A549 lung cancer cells. TKT may be a potential target for the treatment of tumor. DISCLOSURE: The following authors have nothing to disclose: Huili Zhu, Huan Lu No Product/Research Disclosure Information

Up to now,one transketolase (TKT) and two transketolase-like genes (TKTL1 and TKTL2) have been identified in the human genome.People have conducted a series of basic and clinical researches of TKTL1 in malignant neoplasms since Coy found TKTL1 has a high expression of protein and gene levels in the malignant tumors in 2005.Although the biochemical and functional mechanism have not been clarified clearly,a positive role of TKTL1 in promoting tumorigenesis and tumor progression has been proved.

<正>代谢组学(metabonomics/metabolomies)是近年来发展很快的一门新学科,与基因组学、蛋白质组学、转录组学一起构成了生物系统学,在后基因时代的研究已成为热点。代谢组学处于基因组和蛋白质组的下游,是基因组和蛋白质组的补充,能够更为灵敏地鉴定出基因改变、疾病和环境因素作用所产生的特定代谢型(metabotype)。随着各大检测分析技术的发展和联用,使得代谢组学在生命科学诸多领