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Journal: Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases

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Objective: To analyze the outcome of standardized management on the hospitalized asthmatic patients in the past 10 years in a single center. Methods: Clinical data of 2 207 asthmatic patients, who were hospitalized in the Center of Respiratory Medicine and Allergic Diseases, the General Hospital of Northern Military District from January 1, 2008 to December 31, 2017, was retrospectively collected and analyzed. Results: Asthmatic in-patients accounted for 11.5% of total hospitalized patients(2 207/19 134) over the 10-year study period. The highest percentage of asthmatic patients over the total hospitalized patients (16.9%, 207/1 223) was in the year 2008, and it was gradually reduced from 2009 through 2017: a median of 13.2% (221/1 674) from 2009 to 2013 with 3.7% decrease, and a median of 9.4% (224/2 385) from 2014 to 2017 with 7.5% decrease. There was a significant difference in the percentages between the year of 2008 (16.9%) and the years from 2009 through 2017 (P<0.05). Over the 10-year study period, 69.1% (1 526/2 207) of the asthmatic in-patients were hospitalized only once, 13.3% (294/2 207) were twice, and 3.8% (85/2 207) were hospitalized more than twice. Totally 1,553 patients were hospitalized with acute asthmatic attack, which accounted for 8.1% (1 553/19 134) of the total in-patient number over the 10 years, and 14.2% (174/1 223) of which was in the year 2008, while 9.7% (163/1 674) was in the years from 2009 through 2013 with a decrease of 4.5% from 2008, and 5.9% (141/2 385) was in 2014 through 2017 with a decrease of 8.3% from 2008. The differences between the 2008 incidence and that of 2009-2013 or 2014-2017 were statistically significant (P<0.05). However, the incidence of acute exacerbation of comorbid conditions was lowest in 2008 (15.9%, 33/207), while it was 25.8% (58/221) from 2009 to 2013 with an increase of 9.9% from 2008, and 37.0% (83/224) from 2013 to 2017 with an increase of 21.1% compared to 2008. Asthmatic hospitalization peaked in March (9.2%, 150/1 628) and August (9.7%, 157/1 612), respectively, while it was lowest in February (7.1%,101/1 423). The difference between the peak months (March and August) and February was statistically significant (P<0.05), while there was no significant difference between February and the rest of months (P>0.05). When the risk factors for acute asthmatic attack was analyzed by grouping single-time attack (n=1 074) versus multiple-time attack (hospitalized ≥ 2 times, n=479), we found the following risk factors were significant: airway infection (OR=2.006), male (OR=1.355), age ≥ 65 years old (OR=1.364), wet rales on physical examination (OR=1.762), hospitalization ≥ 14 days (OR=1.892), and invasive mechanical ventilation (OR=1.798). In addition, there were significant differences in per capital cost comparison between the following pairs (P<0.05): multiple-time (16 219±16 628, n=681) vs single-time asthmatic hospitalization (13 752±20 692, n=1 526), multiple-time (13 933±13 036, n=479) vs single-time hospitalization with acute asthmatic attack (11 208±13 853, n=1 074), multi-time asthmatic hospitalization (n=681) vs multi-time hospitalization with acute asthmatic attack (n=479), and single-time asthmatic hospitalization (n=1 526) vs single-time hospitalization with acute asthmatic attack (n=1 074). Conclusions: Standardized management of asthma could significantly reduce the risk of hospitalization as well as acute asthmatic attack. Findings of the current study suggested that risk factors for acute and recurrent asthmatic attack should be assessed and managed efficiently in order to reduce incidence of multiple hospitalization for asthma.

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Objective: To investigate the effects of 3-methyladenine on airway inflammation, airway hyperresponsiveness and mucus secretion in asthmatic mice, and to explore its mechanism. Methods: C57BL/6J female mice were randomly divided into normal control group (PBS), OVA group(OVA), OVA with 3-methyladenine group (OVA+3-MA), and OVA with 4-phenylbutyrate group (OVA+4-PBA). OVA group, OVA+3-MA group and OVA+4-PBA groups were all sensitized and challenged with OVA to establish asthmatic models, while PBS group was given PBS as a control. At 2 h before challenge, OVA+3-MA group was intraperitoneally injected with 3-methyladenine, and OVA+4-PBA group was intraperitoneally injected with 4-phenylbutyrate. Airway hyperresponsiveness, eosinophils, and pathological changes of pulmonary tissue (hematoxylin-eosin, HE staining) were measured to confirm the establishment of asthmatic models. Sections of pulmonary tissue were also stained with Masson and PAS. The expression level of LC3B was measured by immunofluorescence and Western blot. The Beclin1, Muc5ac, Atf6, Chop and Bip proteins in lung tissues were detected by Western blot. Results: The Penh value, and eosinophils in BALF in OVA group was significantly increased compared with PBS group (P<0.05). The Penh value in OVA+3-MA group and OVA+4-PBA group were significantly decreased compared with the OVA group at the concentration of 6.25 g/L, 12.50 g/L, 25.00 g/L, and 50.00 g/L of methacholine (all the P<0.05), and the eosinophils were also significantly decreased compared with the OVA group (P<0.05). Pulmonary histology revealed that OVA group showed high levels of inflammatory cell infiltration of bronchi and lung vessels, alveolar septal thickening, structural destruction, smooth muscle thickening, collagen deposition, and goblet cell hyperplasia. The levels of inflammatory cell infiltration of bronchi and lung vessels, alveolar septal thickening, structural destruction, smooth muscle thickening, collagen deposition, and goblet cell hyperplasia in OVA+3-MA group and OVA+4-PBA group were significantly lower than the OVA group, while the PBS group was normal. Compared with PBS group, the expression of LC3 Ⅱ/Ⅰ, Beclin1, Muc5ac, Atf6, Chop and Bip proteins in lung tissues in the OVA group were significantly increased (1.09±0.04 vs 0.34±0.09, P<0.05; 0.18±0.01 vs 0.06±0.01, P<0.05; 1.90±0.38 vs 0.46±0.11, P<0.05; 1.67±0.18 vs 0.41±0.08, P<0.05; 2.96±0.45 vs 1.11±0.10, P<0.05; 2.07±0.34 vs 0.49±0.17, P<0.05, respectively). Compared with the OVA group the expression of LC3 Ⅱ/Ⅰ, Beclin1, Muc5ac, Atf6, Chop and Bip proteins in lung tissues in the OVA+3-MA group and OVA+4-PBA group were significantly decreased (0.46±0.07 vs 1.09±0.04, 0.63±0.03 vs 1.09±0.04, both P<0.05; 0.11±0.02 vs 0.18±0.01, 0.12±0.02 vs 0.18±0.01, both P<0.05; 0.72±0.22 vs 1.90±0.38, 0.57±0.13 vs 1.90±0.38, both P<0.05; 1.06±0.12 vs 1.67±0.18, 1.02±0.12 vs 1.67±0.18, both P<0.05; 1.67±0.21 vs 2.96±0.45, 1.10±0.15 vs 2.96±0.45, both P<0.05; 1.03±0.11 vs 2.07±0.34, 0.97±0.10 vs 2.07±0.34, both P<0.05). Conclusion: 3-MA was shown to inhibit airway inflammation, airway hyperresponsiveness and mucus secretion in mice with bronchial asthma, and the mechanism may be related to inhibiting autophagy, and then inhibiting endoplasmic reticulum stress.

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Objective: To improve the understanding of pulmonary involvement of extranodal natural killer/T-cell lymphoma (ENKTL) by analyzing the clinical manifestations, imaging and pathological features of this disease. Methods: Three cases of ENKTL, proven by pathological diagnosis in Fuzhou General Clinical Medical College of Fujian Medical University, were retrospectively analyzed. Results: All of the 3 cases were males, aged 74, 61 and 49 years, respectively. The main clinical symptoms included cold and fever. One patient had nasal congestion and runny nose. Chest CT showed multiple lung nodules (n=3), masses (n=2) and patchy shadows (n=2), with irregular lesions and clear boundaries. The 3 cases had been misdiagnosed as community acquired pneumonia, and treated with intravenous injection of moxifloxacin. ENKTL was confirmed by CT-guided percutaneous biopsy with immunohistochemical staining, which showed that 3 cases were positive for CD(56), CD(2), in situ hybridization for EBV encoded RNA (EBER), while negative for CD(20), and 2 cases were positive for CD(3), Granzyme B; and 1 case was positive for T-cell intracytoplasmic antigen-1. All 3 patients received chemotherapy, but 2 patients died, one of rejection 1 month later after bone marrow transplantation. One patient had improved after chemotherapy with follow-up. Conclusion: ENKTL should be considered when patients presented with fever, multiple lung nodules or consolidations which were non-responsive to antibiotics. Lung biopsy was the key to diagnosis.

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Objective: To explore the role and mechanism of 2-deoxyglucose (2-dg) in reversing osimertinib- acquired resistance of non-small cell lung cancer(NSCLC)cell line. Methods: The NSCLC line H1975 (purchased from the American Type Culture Collection) was conducted by induction method in vitro to construct the osimertinib-resistance NSCLC cell line H1975-OR. The osimertinib-resistance of H1975-OR cell line was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony-formation assay, Ki67 incorporation assay and the expression of apoptosis-related protein. The glycolysis level was assayed by the lactic acid production measured in the culture medium supernatant of H1975 and H1975-OR. The expression of glycolysis key enzymes (HK2, GLUT1, P-PKM2) and apoptosis-related protein (BIM, Bcl-2) were detected by Western blot. The cells were divided into control group, 2-deoxyglucose (4 mmol/L) monotherapy group, osimertinib (3 μmol/L) monotherapy group and 2-deoxyglucose (4 mmol/L)+ osimertinib (3 μmol/L) combination therapy group, then the apoptosis rate of cells was measured by flow cytometry to evaluate the pro-apoptotic ability of drugs. Date were analyzed by Independent-Samples t-test using SPSS 16.0 statistical software. Results: The glycolysis level of osimertinib-sensitive cell line H1975 was lower than that of osimertinib-resistance cell line H1975-OR [the yield of lactic acid, respectively, was (21.0±0.9) and (26.5±2.8) mmol·L(-1)·10(4)cells(-1), P<0.05]. The osimertinib- acquired resistance of H1975-OR could be reversed by 4 mmol/L 2-deoxyglucose(the IC(50) value of osimertinib in H1975-OR cell line decreased from (7.0±1.9) μmol/L to (1.4±0.1) μmol/L, which was close to the IC(50) value of osimertinib in H1975 cell line (1.0±0.2) μmol/L. The apoptosis rate of H1975-OR was significantly higher in 2-deoxyglucose + osimertinib combination therapy group (26.7±2.4)%, compared to control group (5.1±0.7)%, 2-deoxyglucose monotherapy group (6.1±2.5)% and osimertinib monotherapy group (11.4±2.7)%(all P<0.05). The expression of pro-apoptotic protein BIM in H1975-OR was significantly higher in 2-deoxyglucose+ osimertinib combination therapy group (177.8±28.1)% and the expression of anti-apoptotic protein Bcl-2 in H1975-OR was significantly lower in 2-deoxyglucose+ osimertinib combination therapy group (24.6±5.2)%, compared to control group (100±0)%, all P<0.05. Conclusion: 2-deoxyglucose can reverse the acquired resistance of NSCLC cell line to osimertinib, which may be related to the inhibition of cell glycolysis and the induction of apoptosis.

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Objective: To better understand the clinical features of human adenovirus type 7 (hAdV7) pneumonia and to identify whether there is a variation in the genome of the strain (CHN/BeiJing/2018) isolated during the small-scale epidemic. Method: Forty-two patients were diagnosed with hAdV7 pneumonia between October 27th, 2017 and February 28th, 2018. They were all males with an average age of (21±2) years. Demographic and clinical data were reviewed and analyzed in detail. The nucleic acid of the epidemic strain was extracted from a bronchoalveolar lavage fluid sample. Whole genome sequencing (WGS) was then performed and sequences were compared with other hAdV7 strains distributed globally. Phylogenetic tree analysis was conducted based on whole genome sequences of the epidemic strain. Results: Thirty-eight cases with hAdV7 pneumonia presented with influenza-like symptoms (90.5%) at the onset and 36 cases developed fever (85.7%), followed by cough (97.6%), expectoration (90.5%) and chest pain (28.6%). Five cases presented with tonsillitis(11.9%) and 4 had transient hemoptysis (9.5%), while 3 patients reported dyspnea (7.1%). Moist rales were only heard in 3 patients (7.1%). Notably elevated creatine kinase (CK) concentrations were observed in 8 patients (19.1%), but all returned to normal after treatment. Four cases developed hypoxemia (9.5%), but none of them progressed to respiratory failure or acute respiratory distress syndrome (ARDS). Chest CT imaging showed bilateral patchy parenchymal opacities with a random distribution with or without consolidation. Ten patients were co-infected with influenza virus (23.8%), while 32 patients developed atypical pneumonia (76.2%). Genomic analysis revealed that the strain isolated during this epidemic was 99% similar to the known hAdV7 strains (19BOVLB/Volgograd/Rus/2014 and 0901HZ/ShX/CHN/2009). Phylogenetic tree analysis suggested that the strain was closely related to the hAdV7 strain isolated in Jingmen China in 2012. Conclusions: Cases with hAdV7 pneumonia were generally mild. Symptomatic treatment was sufficient for a favorable prognosis. A good genome stability of the hAdV7 strain was observed, indicating that hAdV7 could remain stable for a long period and cause continuing sporadic cases and clusters.

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Objective: To assess the quality of the clinical practice guideline for diagnosis, treatment and prevention of pulmonary thromboembolism, 2018 in China, providing the references for updating and developing clinical practice guidelines of this field in the future. Methods: The quality of the clinical practice guideline for diagnosis, treatment and prevention of pulmonary thromboembolism, 2018 in China was assessed using the internationally recognized instrument Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ). AGREE Ⅱ instrument consisted of 23 items in six domains, followed by two overall assessment items. Each item was scored from 1 to 7. The final overall guideline quality considered all domain items. Results: The scores of the six AGREE Ⅱ domains were: Scope and purpose 76.4%, Stakeholder involvement 55.6%, Rigor of development 78.1%, Clarity and presentation 83.3%, Applicability 55.2%, and Editorial independence 66.7%. The guideline was recommended for clinical use. Among the 101 recommendations, recommendations based on Levels High, Moderate and Low evidence accounted for 7 (6.9%), 31 (30.7%) and 63 (62.4%), respectively. Conclusion: The methodological quality of the clinical practice guideline for diagnosis, treatment and prevention of pulmonary thromboembolism, 2018 in China was great, but the levels of evidence were not high. More efforts were urgently required to improve in Stakeholder involvement and applicability. Especially corresponding economic research evidence, as well as preferences of patients and the public should be considered in the future development of clinical practice guidelines.

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Objective: To investigate the clinical significance of recombinant virus-specific detection for detecting viable circulating tumor cell (CTC) in lung cancer patients. Methods: From June 2017 to August 2018, 63 lung cancer patients diagnosed by imaging and pathology at the Department of Respiratory and Critical Care Medicine, Beijing Anzhen Hospital were recruited for this study, including 38 cases of adenocarcinoma, 13 squamous cell carcinoma, and 12 small cell carcinoma. The patients consisted of 36 males and 27 females, with an average age of (65±11) years. In addition,21 patients with benign lung diseases were recruited for benign lung disease group, including 11 males and 10 females with an average age of (57±13) years. Another 18 healthy subjects were recruited for the healthy control group, including 10 males and 8 females, with an average age of (32±10) years. The peripheral blood viable CTCs were detected by a CTC in vitro detection kit containing recombinant virus. Fisher’s exact test was used to compare the differences between the groups of viable CTC positive rates. Results: Cases with positive viable CTC in the lung cancer group, the benign lung disease group and the healthy control group were 56,4 and 0, respectively. The sensitivity and specificity of this CTC detection system were 89% (56/63) and 90% (35/39) , respectively. The positive rate of CTC detection for lung cancer patients with adenocarcinoma, aquamous cell carcinoma, and small cell carcinoma, were 84%(32/38), 92% (12/13) and 100% (12/12), respectively. The positive cases from adenocarcinoma and squamous cell carcinoma patients with different stages were 2 (n=2) in stageⅠ,6 (n=8) in stage Ⅱ,7(n=8) in stage Ⅲ and 29(n=33) in stage Ⅳ. There were no significant differences in the positive rates of CTC among different histological types or different stages (χ(2)=1.881, 3.419; P>0.05) . Conclusion: This CTC detection system was found to be a simple and non-invasive method for auxiliary diagnosis of lung cancer, with high sensitivity and specificity.

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Objective: This study aimed to explore a feasible method of anesthesia for painless bronchoscopy. Methods: A total of 120 patients receiving flexible bronchoscopy in Beijing Tiantan Hospital during the period from February, 8, 2018 to May, 4, 2018, were randomly divided into 3 groups, including group A (using lidocaine for local anesthesia), group B (using lidocaine + midazolam + fentanyl), and group C (using lidocaine + propofol + sufentanil). There were 41 patients in group A, 38 in group B and 41 in group C. The changes in systolic blood pressure, diastolic blood pressure, heart rate and pulse oxygen saturation(SpO(2)) in each group were recorded in different points of time. The safety of different methods of anesthesia was observed by recording vital signs and adverse events. Moreover, the visual analogue scale (VAS) was used to observe the patient’s tolerance and satisfaction of the operation. Results: The intraoperative systolic blood pressure and diastolic blood pressure in group C were significantly lower than those in group A and B (P<0.05). Six cases in group C had hypotension, 3 of whom required vasoactive drugs. The differences of SpO(2) between the 3 groups showed no statistical significance (P>0.05), while patients in group C were prone to decrease in SpO(2). Eighteen patients in group C had hypoxemia during operation. But after treated with improving ventilation, the SpO(2) of those patients could be restored to normal. Compared with those in group C, patients in group A and group B showed significant discomfort, cough, and more pharyngeal pain (P<0.05). However, there were no significant differences in the degree of cough and pain between group A and group B (P>0.05). Most patients in group C had no uncomfortable sensation during the operation (P<0.05), and the willingness to re-examination was significantly higher than that in group A and group B (P<0.05). Conclusion: Propofol combined with sufentanil could achieve better painless effect, improve patient comfort and tolerance, and reduce intraoperative memory, but was prone to causing hypoxemia and hypotension. The decline of intraoperative SpO(2) could be corrected by establishing artificial airway, while the decrease of blood pressure could be corrected by applying vasoactive drugs, which were relatively safe.

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Objective: To describe the clinical characteristics of acute respiratory distress syndrome (ARDS) caused by severe influenza virus in our hospital. Method: From November 2017 to February 2018, 48 patients were diagnosed with ARDS caused by influenza virus pneumonia. There characteristics, treatment, and outcomes were summarized and analyzed. According to the prognosis, the patients were divided into a survival group and a death group for comparative analysis. The multivariable logistic regression analysis was used for risk factors of hospital mortality. Result: Thirty-one patients were confirmed to have influenza A virus infection, 3 influenza B virus, 2 mixed infection, while 12 patients were diagnosed by clinical criteria. Eighteen patients died, with a mortality of 38%. Twenty-six patients (54%) were co-infected by other pathogenic microorganisms, including 17 cases of invasive aspergillus infection. Sixteen patients (33%) acquired nosocomial infection that significantly correlated with the hospital mortality, P=0.003. Multivariable logistic regression analysis showed that higher age (OR=1.086, 95% CI: 1.016-1.016), P=0.015), longer duration of flu-like symptoms to RICU time (OR=1.196, 95% CI: 1.031-1.031, P=0.018) and lower PaO(2)/FiO(2) (OR=0.973, 95% CI: 0.951-0.951, P=0.017) were independent risk factors for hospital mortality. Conclusion: In the flu season of 2017-2018, the patients of ARDS caused by severe influenza pneumonia were mainly influenza A virus, with a mortality of 38%. Co-infection was very common, especially aspergillus infection. Nosocomial infection was common and significantly correlated with high mortality. Lower PaO(2)/FiO(2), higher age and the longer duration from influenza-like symptoms to RICU was independent risk factors for high hospital mortality.

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Objective: To analyze the clinical manifestations of patients with endobronchial hamartoma(EH),and therefore to improve understanding of the disease. Methods: Data were retrospectively reviewed to describe the clinical characteristics, diagnosis procedures and prognosis of EH, including 5 patients in Beijing Anzhen Hospital, Capital Medical University from Jun 2007 to Feb 2018 and another 159 patients from Chinese and English literatures published after Jan 2000. Results: The five patients, 4 males and 1 female, aged from 46 to 69 years[mean (56±7) years], were diagnosed with EH in our hospital. There was no fever in the 5 cases, cough and expectoration in 4 cases, hemoptysis in 3 cases and asymptomatic in 1 case. Chest CT revealed that the lesions of all 5 cases were located in the right bronchial tube; 3 as high-density endobronchial mass, 1 as low-density mass, 1 as mixed density mass, and 1 as a “popcorn” lesion. Three cases were accompanied by obstructive pneumonia in the distal part of the EH and 2 cases by atelectasis. CT enhanced scan was performed in 5 cases, 2 showing no enhancement and 3 showing mild enhancement. Four cases showed polyposis under bronchoscopy, and 5 cases received bronchoscopic biopsy with 3 pathologically diagnosed as EH. Four of them received lobectomy, while 1 received removal by biopsy forceps, and all were pathologically confirmed as EH. There was no evidence of recurrence in these 5 patents with follow-up. Conclusions: EH was a rare benign bronchial tumor with nonspecific clinical and imaging manifestations. Endobronchial polyposis could be revealed by bronchoscopy, and pathological study is required to confirm the diagnosis.