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BACKGROUND: The cuff leak test (CLT) has been shown to have excellent specificity and moderate sensitivity for predicting postextubation stridor (PES). However, the ventilator flow waveform and the subject position are not uniform in current clinical practice. METHODS: We conducted a prospective cohort study in the respiratory ICU of the Beijing Chaoyang Hospital, Capital Medical University. Prior to extubation, 4 CLTs, combining 2 different postures and ventilator flow waveforms, were conducted, and the diagnostic performance of each test was assessed. RESULTS: Of the 143 included subjects, PES occurred in 13 (9.1%), and 10 (7%) subjects required re-intubation. Initially, an air leak volume of 110 mL was used as the standard to judge performance. The test that involved the square waveform and the subject in semi-recumbent position (test 4) had the best diagnostic performance, with a specificity of 80% and a sensitivity of 67% for predicting PES. After analyzing the receiver operating characteristic curve, an optimal diagnostic threshold of 116 mL for air leak volume was found to result in a specificity of 92% and a sensitivity of 63% for test 4. Additionally, when the air leak ratio of test 4 was 0.32, the area under the curve was 0.76, the specificity was 92%, and the sensitivity was 62%. CONCLUSIONS: In this study, performing the CLT with the subject in semi-recumbent position using the square waveform appeared to allow for the best prediction of PES.

Sickle cell disease (SCD) is a single gene genetic disease, which seriously threatens the life span and quality of patients. On the basis of the pathogenesis of SCD and the alternative therapy based on fetal hemoglobin F (HbF), the research progress of transcription factors involved in the regulation of HbF gene expression, such as BCL11A, ZBTB7A, KLF-1, c-MYB and SOX6, as well as the application of CRISPR / Cas9, TALEN, zinc finger nuclease and other gene editing technologies in this field has been made, providing a solid theoretical basis for the exploration of new treatment schemes for β- like hemoglobin diseases, such as sickle cell disease and β- thalassemia.基于血红蛋白F的镰状细胞病基因治疗的研究进展.镰状细胞病（SCD）是一种单基因遗传病，严重威胁患者寿命和生活质量。本文从SCD的发病机制及基于胎儿血红蛋白F（HbF）的替代治疗入手，回顾了近年对BCL11A、ZBTB7A、KLF-1、c-MYB和SOX6等参与HbF基因表达调控的转录因子的研究进展，以及CRISPR/Cas9、TALEN、锌指核酸酶等基因编辑技术在该领域的应用，为SCD及β-地中海贫血等β-样血红蛋白病的新治疗方案的探索提供坚实的理论基础.

Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses.The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS.This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared.The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P .05). The PaoThere were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

Multidrug resistance (MDR) is a serious obstacle to cancer chemotherapy. Overexpression of P-glycoprotein (P-gp), the MDR1 gene product, confers MDR to tumor cells. This study explored the possibility of reducing drug resistance by targeting the mdr1 gene using short hairpin RNA (shRNA). Two different shRNAs were designed and constructed in a pSilencer 2.1-U6 neo plasmid. The shRNA recombinant plasmids were transfected into HT9 leukemia cells. Real-time polymerase chain reaction and Western blotting were used to characterize the inhibited expression of MDR1 mRNA and P-gp, and the drug sensitivity of the transfected cells was assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The results indicated that the inhibition of P-gp expression by small interfering RNA selectively restored sensitivity to the drugs transported by P-gp. Evaluation of chemosensitivity showed 52.58% reversal by p2.1-shRNA1 and 73.07% reversal by p2.1-shRNA2 in drug resistance for harringtonine, and 84.87% reversal by p2.1-shRNA1 and 94.23% reversal by p2.1-shRNA2 in drug resistance for curcumin in the transfected cells. The results demonstrated the efficacy and selectivity of shRNA in reversing MDR in drug-resistant HT9 cells in vitro.

This study aims to identify morphological changes in the lung parenchyma of acute respiratory distress syndrome (ARDS) survivors after extracorporeal membrane oxygenation (ECMO) by high-resolution computed tomography (HRCT) follow-up. Factors influencing these changes are also examined.Information and lung HRCT scans were collected and studied 1, 3, 6, and 12 months after the withdrawal of severe ARDS survivors rescued by ECMO in the Respiratory Care Unit of Beijing Chaoyang Hospital from November 2009 to August 2012. The observation endpoint was set as the time when the lung lesions were basically absorbed or 12 months after withdrawal.Among nine survivors, one survivor was lost to follow-up. The lesions of two patients, which were attributed to bacterial pneumonia and pneumocystis pneumonia, were basically absorbed 1 month after surgery. Six patients completed the 12 month follow-up. Although initial morphological changes varied, different degrees of absorption improvement were observed in later stages of treatment. Lung HRCT analysis on the sixth month indicated that the degree of involvement of the ventral region was greater than that of the dorsal area. No significant difference was observed in patients in terms of ECMO support time, pre-ECMO Murray score, and APACHE II score, among others.Lung HRCT of severe ARDS survivors after ECMO treatment showed various degrees of morphological changes in the lung parenchyma. The severity of these changes may be associated with the disease duration.

To summarize the experience of extracorporeal membrane oxygenation (ECMO) for patients with severe acute respiratory failure in adults and to investigate the factors associated with death.The clinical data of patients with severe acute respiratory failure supported with ECMO in respiratory intensive care unit of Beijing Chaoyang Hospital from November 2009 to December 2011 were prospectively collected and analyzed. The data included general condition before EMCO, blood gas analysis, hemodynamics, ventilator settings of mechanical ventilation and complications during ECMO. The primary outcome was death or severe disability within 3 months. Statistical software of SPSS (version 16.0) was used for data analysis.Twenty-five patients with severe respiratory failure received ECMO treatment, of which 16 patients were analyzed. The mean age was (45 ± 14) years old (range, 22 - 64 years old). Thirteen patients were male. Before ECMO, all of the patients were treated with invasive positive pressure ventilation for (72 ± 64) hours. Eight patients had been treated with noninvasive ventilation for a median of 55(10-114) hours. Patients had severe respiratory failure despite advanced mechanical ventilator support. The mean PaO2/fraction of inspired oxygenation (FiO2) ratio was (54 ± 18) mm Hg (1 mm Hg = 0.133 kPa), positive end-expiratory pressure (PEEP) was (11 ± 6) cm H2O(1 cm H2O = 0.098 kPa), Murray lung injury score was 3.6 ± 0.5, serum lactate was (2.5 ± 2.0) mmol/L, serum white blood cell count was (16 ± 6)×10(9)/L, and APACHEII score was 17 ± 8. All of the patients were treated with venous-venous ECMO (VV-ECMO). The change of mechanical ventilation settings were (pre-ECMO vs 2 hours post-ECMO): FiO2 1.0 vs 0.55 ± 0.21, PEEP (11 ± 6) vs (9 ± 6) cm H2O, V(T) (6.8 ± 2.2) vs (4.4 ± 2.0) ml/kg PBW, peak airway pressure (27 ± 8) vs (24 ± 7) cm H2O, respiratory rate (37 ± 10) vs (23 ± 10) breaths/min. Arterial blood gas, including pH, PaO2 and PaCO2 were significantly improved after ECMO running 24 and 48 hours (P0.05). The mean VV-ECMO support interval was (9.7 ± 9.6) days (range, 2 - 41 days). Ten patients were successfully weaned from ECMO, of whom 2 died in ICU. Three patients died during ECMO, while another 3 patients died after withdrawal of further treatment. Eight patients survived to 3 months without severe disability. In a multi-variate Cox regression model, pre-ECMO factors including lower PaO2/FiO2 and increasing white blood cell count were associated with increased risks of death (RR was 0.733, 1.701 respectively, both P values0.05).VV-ECMO is a potentially effective approach for severe acute respiratory failure. PaO2/FiO2 and white blood cell count pre-ECMO may be the risk factors for poor outcome.

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is always associated with a high incidence and mortality. Because of the presence of some concomitant risk factors such as immobilization, bronchial superinfection, patients who are admitted for acute exacerbations of COPD are generally considered to be at moderate risk for the development of venous thromboembolism. In this study, we investigated the prevalence and the clinical manifestations of deep venous thrombosis (DVT) in patients with acute exacerbation of COPD.From March 2007 to March 2009, 520 consecutive patients were included in this study. On admission, color Doppler ultrasound of lower extremities in all cases was performed for diagnosing DVT. Patients with DVT were compared with those without DVT from such aspects as demographics, symptoms, physical signs and risk factors.Among the 520 patients, DVT was found in 46 cases (9.7%). In patients with DVT, the duration of hospitalization was longer (P = 0.01), and the mechanical ventilation requirement increased (P0.001). Other indicators for patients with more possibility of DVT were immobility exceeding 3 days (P0.001); pneumonia as concomitance (P = 0.01); respiratory failure type II (P = 0.013); current smoking (P = 0.001). Lower extremity pain was more common in DVT cases in comparison to those without DVT (34.8% vs. 15.2%, P = 0.01).The acute exacerbation of COPD patients, who were immobilized for over 3 days, complicated by pneumonia and had respiratory failure type II, had a higher risk of DVT. In addition, DVT detection awareness should be increased in cases that had a lower extremity pain.

Overexpression of P-glycoprotein (P-gp), the mdr1 gene product, confers multidrug resistance (MDR) to tumor cells and often limits the efficacy of chemotherapy. This study evaluated RNAi for specific silencing of the mdr1 gene and reversion of multidrug resistance. Three different short hairpin RNAs (shRNAs) were designed and constructed in a pSilencer 3.1-H1 neo plasmid. The shRNA recombinant plasmids were transfected into HT9 leukemia cells. The RNAi effect was evaluated by real-time PCR, Western blotting and cell cytotoxicity assay. In the cell, shRNAs can specifically down-regulate the expression of mdr1, mRNA and P-gp. Resistance against harringtonine, doxorubicin and curcumin was decreased. The study indicated that shRNA recombinant plasmids could modulate MDR in vitro.

To establish human integrin-alpha v adenovirus expressed in human liver cancer SMMC-7721 cells and analyze the characteristics of integrin-alpha adhesion to liver cancer cells.Human integrin-alpha v cDNA was cloned into the plasmid pAdTrack-CMV. Then, pAdTrack-integrin-alpha v was cotransformed with adenoviral backbone vector into E. coli strain BJ5183. The recombinant adenoviral plasmid was identified by restriction analysis with Pac I and transfected into HEK-293A cells to package and amplify recombinant adenovirus particles. Western blot showed that integrin-alpha v gene was exactly transcript and expressed in SMMC-7721 cells. Twenty four hours after transfection, the effect of integrin-alpha on adhesion of SMMC-7721 cells was detected by adhesion experiment.Recombinant adenovirus vector of integrin-alpha v gene was successfully constructed and high titers of recombinant adenovirus was obtained. Adhesion cell count was significantly higher in integrin-alpha v transfected cells than in untransfected and Ad-null-transfected cells (P0.01).Over expression of integrin-alpha v promotes adhesion of SMMC-7721 cells, is an important molecular mechanism of tumor metastasis.