Integrated bioinformatics analysis of microarray data from non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), with its high mortality rate, lack of early diagnostic markers and prevention of distant metastases are the main challenges in treatment. To identify potential miRNAs and key genes in NSCLC to find new biomarkers and target gene therapies. The GSE102286, GSE56036, GSE25508, GSE53882, GSE29248 and GSE101929 datasets were obtained from the Gene Expression Omnibus (GEO) database and screened for differentially co-expressed miRNAs (DE-miRNAs) and lncRNAs (DElncRs) by GEO2R and R software package. Pathway enrichment analysis of DE-miRNAs-target genes was performed by String and Funrich database to construct protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) network and visualized with Cytoscape software. Nineteen co-expressed DE-miRNAs were screened from five datasets. The 7683 predicted up- and down-regulated DE-miRNAs-target genes were significantly concentrated in cancer-related pathways. The top 10 hub nodes in the PPI were identified as hub genes, such as MYC, EGFR, HSP90AA1 and TP53, MYC, and ACTB. By constructing miRNA-hub gene networks, hsa-miR-21, hsa-miR-141, hsa-miR-200b and hsa-miR-30a, hsa-miR-30d, hsa-miR-145 may regulate most hub genes and hsa-miR-141, hsa-miR-200, hsa-miR-145 had higher levels in the miRNA and ceRNA regulatory networks, respectively. In conclusion, the identification of hsa-miR-21, hsa-miR-141, hsa-miR-200b hsa-miR-30a, hsa-miR-30d and hsa-miR-145 provides a new theoretical basis for understanding the development of NSCLC.

Research on the evaluation and optimization model of community public space during the epidemic prevention period based on TOPSIS.

Since 2019n-CoV has swept the whole world, people's daily life is affected seriously and the public space system is facing to major challenges. Community public space should be re-evaluated and optimized as people change the way they use it. This research conducted a nationwide questionnaire survey in China, which collected the opinions of residents on community public space from the perspective of epidemic prevention and social needs to select research indicators. The questionnaire data were processed through the frequency analysis method, precedence chart and TOPSIS. We found: (1) under the background of the epidemic, people pay more attention to the satisfaction of leisure activities in community public space and the control of social spacing during activities; (2) the current assessment result of community public space risk of 2019-nCoV exposure is 0.386, which is relatively high; and (3) the exposure risk of the community can be effectively reduced by controlling for the two indicators of social distance and social facility sterilization. When the social distance is 1.8-3 m and the facility sterilization is once a day, the community public space minimizes exposure risk. In view of the above results, this paper selects the Wuhan start-up area of Wuhan, China, as an example for carrying out the optimization design of community public space based on the epidemic and the design the space optimization model for the two indicators of social distance and facility disinfection from both software and hardware aspects.

[Clinical analysis of 150 patients with idiopathic pulmonary arterial hypertension].

OBJECTIVE: To explore the demographic characteristics and clinical features of patients with idiopathic pulmonary arterial hypertension (IPAH) in China. METHODS: Between March 2007 and September 2010, IPAH diagnosis was confirmed by right heart catheterization in 150 adult patients from 31 clinical centers in China. Clinical and hemodynamic data were analyzed and patients were divided into WHO functional class I/II and WHO functional class III/IV group. RESULTS: The mean age of 150 patients were 36 ± 13 years with female patient/male patient ratio of 2:1, and mean BMI was (21.3 ± 3.5) kg/m(2). Fatigue (n = 123, 82.0%) and dyspnea (n = 112, 74.7%) are the most common symptoms. Accentuated pulmonic second sound (P(2)) was detected in 92.0% (n = 138) of patients during physical examination, which was also the most common sign. About 49.0% (n = 73) patients were WHO functional class I/II patients and 46.0% (n = 68) patients were WHO functional class III/IV patients. Six minutes walking distance (6MWD) and Borg dyspnea score was (337 ± 101) m and 2.0 (2.0, 4.0), respectively. Right ventricular hypertrophy was suggested by ECG in 93.1% (n = 140) patients. Right atrial pressure was (10 ± 6) mm Hg, mean pulmonary artery pressure was (61 ± 16) mm Hg, cardiac index was (2.3 ± 0.8) L×min(-1)×m(-2) and pulmonary vascular resistance (1484 ± 699) dyn×s(-1)×cm(-5) in this cohort. 6 MWD (305 m ± 89 m vs. 377 m ± 88 m) was significantly shorter while Borg dyspnea score [3.0 (3.0, 5.0) vs. 2.0 (2.0, 3.0)] was significantly higher in WHO functional class III/IV patients than in WHO functional class I/II patients. Similarly hemodynamic parameters were also worse in WHO functional class III/IV patients than in WHO functional class I/II patients (all P < 0.05). CONCLUSION: Idiopathic pulmonary arterial hypertension patients in this cohort affect mostly young adults, dominated by female gender and lower body mass index. Fatigue and dyspnea are the most common symptoms and accentuated pulmonic second sound (P(2)) is the most common sign. IPAH patients are often displaying severe functional and hemodynamic disturbance at first visit to hospitals. Dyspnea and hemodynamic impairment are related to 6MWD and WHO functional class.

[Multicenter study of disease attributes in adult patients with pulmonary hypertension].

OBJECTIVE: To understand the demographic, hemodynamic and clinical features of adult patients with pulmonary hypertension (PH) in China. METHODS: Between May 2007 and October 2010, a total of 551 adult PH patients were recruited from 31 clinical centers all over China. All fulfilled the traditional hemodynamic criteria diagnosed through right heart catheterization (RHC). The relevant data of demographic, clinical and hemodynamic features of all patients, analyzed the similarities and differences of demographic characteristics between different subtypes. They were divided into 2 groups: WHO functional class I/II and III/IV. And their hemodynamic and clinical features were compared. RESULTS: There were 165 males and 386 females with a mean age of (35 ± 12) years. The mean body mass index (BMI) was (21 ± 4) kg/m(2). There were pulmonary arterial hypertension (PAH, n = 487) and chronic thromboembolic pulmonary hypertension (CTEPH, n = 64). Fatigue (421, 76.4%) and dyspnea (398, 72.2%) were the most common symptoms; Physical examination revealed such a common sign as an accentuated pulmonic second sound (P(2)) in 510 patients (92.6%). Over half (325, 59.0%) of them were of WHO functional class II and 213 (38.6%) patients functional class III. The 6-minute walking distance (6MWD) and Borg dyspnea score were (352 ± 91) m and 3.0 (2.0 - 4.0) respectively. ECG of 497 (90.2%) patients showed right ventricular hypertrophy. Mean right atrial pressure was (9 ± 6) mm Hg (1 mm Hg = 0.133 kPa), pulmonary arterial pressure (67 ± 20) mm Hg, cardiac index (2.7 ± 1.2) Lmin(-1)m(-2) and pulmonary vascular resistance (1496 ± 783) dyn.sec.cm(-5). CONCLUSIONS: Young females with a low BMI are predominantly affected by PH. Severe functional and hemodynamic compromises often appear on presentation. And hemodynamic impairment is correlated with 6MWD and WHO functional class.

Inhaled low-dose iloprost for pulmonary hypertension: a prospective, multicenter, open-label study.

BACKGROUND: Inhaled iloprost (average >30 µg/d) has been considered an effective treatment for severe pulmonary hypertension (PH). Further evidence also showed that low-dose iloprost given intravenously was equally effective as high-dose iloprost in the therapy of systemic sclerosis. HYPOTHESIS: Patients with pulmonary hypertension will benefit from inhalation of low-dose iloprost. METHODS: Sixty-two patients with PH were enrolled and initiated with neubulizedlow-dose iloprost (2.5 µg per inhalation, 6× daily) for 24 weeks in 13 medical centers in China. Efficacy endpoints included changes in 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC), and hemodynamic parameters. RESULTS: Fourteen patients (22.6%) prematurely discontinued the study: 8 due to clinical worsening (6 in WHO-FCIII-IV at baseline), 4 because of protocol change, and 2 patients lost during follow-up. In the remaining 48 patients, 6MWD was increased from 356 ± 98 meters to 414 ± 99 meters (P < 0.001) and WHO-FC improved significantly (P = 0.006) after 24-week inhalation therapy. Cardiac output, cardiac index, and mixed venous oxygen saturation improved significantly compared with baseline (n = 34, P < 0.05). Most of the hemodynamic parameters improved significantly in patients in WHO-FC II (P < 0.05) but not in patients in WHO-FCIII-IV. CONCLUSIONS: Low-dose iloprost inhalation significantly improved exercise capacity and functional status in patients with PH. It was well tolerated. The improvement of hemodynamics was confirmed in patients with WHO-FCI-II but not in patients with WHO-FCIII-IV, suggesting the importance of early treatment in patients with advanced disease stages.

Oral sildenafil therapy for Chinese patients with pulmonary arterial hypertension: a multicenter study.

The impact of sildenafil on pulmonary arterial hypertension (PAH) in Chinese patients has been less investigated. A prospective, open-label, uncontrolled and multicenter study, therefore, was carried out to address this issue. Ninety patients with multicause-induced PAH received oral sildenafil (75 mg/day) for 12 weeks. The 6-minute walk test (SMWT) and cardiac catheterization were performed at the beginning and the end of the 12 weeks. The primary endpoint was the changes in exercise capacity assessed by the SMWT; the secondary endpoint included assessment of functional class, evaluation of cardiopulmonary hemodynamics, and clinical worsening. Drug safety and tolerability were also examined. The results showed that there was a significant improvement in SMWT distances (342 ± 93 m vs 403 ± 88 m, P < .0001), Borg dyspnea score (2.9 ± 2.6 vs 2.4 ± 2.0, P = .0046), World Health Organization functional class, and cardiopulmonary hemodynamics (mean pulmonary artery pressure, P < .0001; cardiac index, P < .0001; pulmonary vascular resistance, P < .0001) after 12 weeks of oral sidenafil therapy. Almost all enrolled patients did not experience significant clinical worsening. This study confirms and extends the findings of previous studies relating to effects of sildenafil on PAH, suggesting that oral sildenafil is safe and effective for the treatment of adult patients with PAH in the Chinese population.

[Sildenafil therapy for pulmonary hypertension: a prospective study].

OBJECTIVE: To explore the safety and efficacy of oral sildenafil therapy for pulmonary arterial hypertension (PAH), and to provide evidence for sildenafil treatment for Chinese patients with PAH. METHODS: In this 12-week, prospective, open-label, uncontrolled study, 56 patients with PAH were given oral sildenafil (25 mg, tid). The primary end point was change from baseline to 12 weeks in exercise capacity assessed by 6 min walk (6MW) test. Secondary end points included changes in WHO class and cardiopulmonary hemodynamics. Clinical worsening was defined as death, transplantation, hospitalization for PAH, or initiation of additional therapies for PAH, such as intravenous epoprostenol or oral bosentan. RESULTS: After 12 weeks, the compliance was good in 56 patients. Significant improvement was seen in NYHA heart function class and WHO class as compared to baseline (P < 0.01): from class IV to class III in 2, from class III to class II in 8 and to class I in 2 cases, and from class II to class I in 5 cases. No NYHA heart function class and WHO PAH function class deterioration were observed. Oral sildenafil increased 6MW distance, from (352 ± 80) m to (396 ± 78) m, with a change of (44 ± 70) m (P < 0.01). Significant improvement was seen in hemodynamics (mean pulmonary artery pressure, P < 0.01; cardiac index, P < 0.01; pulmonary vascular resistance, P < 0.01) at week 12 as compared with baseline. Mean right atrial pressure decreased (3 ± 11) mm Hg (1 mm Hg = 0.133 kPa), mean pulmonary arterial pressure decreased (6 ± 14) mm Hg, cardiac output increased (1.1 ± 2.0) L/min, cardiac index increased (0.7 ± 1.1) L×min(-1)×m(-2), and total pulmonary resistance decreased (490 ± 831) Dys×s×cm(-5). Side effects were mild and consistent with those reported with sildenafil treatment. No statistically significant clinical worsening was observed with sildenafil therapy for PAH patients. CONCLUSIONS: Sildenafil improves exercise capacity, WHO functional class, and hemodynamics in patients with pulmonary arterial hypertension.

The efficacy and safety of sildenafil in patients with pulmonary arterial hypertension associated with the different types of congenital heart disease.

BACKGROUND: The difference in underlying pathophysiology in different congenital heart disease (CHD) may have an influence on clinical outcome. It remains unclear whether the effect of sildenafil on pulmonary arterial hypertension (PAH) varies in different types of CHD. HYPOTHESIS: The potential effect of sildenafil on pulmonary arterial hypertension related to CHD may be associated with shunt location. METHODS: In this 12-week, prospective, open label, multicenter trial, 55 patients with CHD were divided into the 3 groups: atrial septal defects group (ASD, n = 15), ventricular septal defects group (VSD, n = 24), and patent ductus arteriosus group (PDA, n = 16). Exercise capacity, hemodynamic parameters, and arterial oxygen saturation were assessed at baseline and after sildenafil therapy (25 mg, 3 times daily). RESULTS: Six-minute walk distance significantly increased from 377.2 ± 68.7 m to 436.0 ± 70.4 m in patients with ASD, from 371.2 ± 66.0 m to 413.7 ± 83.1 m in VSD, and from 384.3 ± 90.2 m to 440.9 ± 71.8 m in PDA (P<0.01, respectively). Moreover, sildenafil also improved the pulmonary vascular resistance and pulmonary blood flow index in the 3 groups, whereas no significant changes in systemic vascular resistance and systemic arterial pressure were observed. However, arterial oxygen saturation was significantly improved in the ASD group only. The incidence of adverse events was similar among the 3 groups. CONCLUSIONS: Sildenafil therapy seems to be effective and safe for PAH secondary to ASD, VSD, and PDA, although some clinical and hemodynamic parameters were changed in a different manner among the 3 groups.

[Preliminary study on the efficacy and safety of oral sildenafil in pulmonary arterial hypertension in China].

OBJECTIVE: Sildenafil has been shown to be effective in pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH has been under-investigated in China. The aim of the present study was to evaluate the efficacy and safety of oral sildenafil in PAH patients in China. METHODS: In this prospective, open-label and multi-center study, 90 patients were recruited from 14 centers to receive oral sildenafil (75 mg/d) for 12 weeks. They underwent a six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of 12 weeks. The primary endpoint was the changes in exercise capacity as assessed by SMWT. And the secondary endpoints included assessment of functional class, evaluation of cardiopulmonary hemodynamics and clinical deterioration (defined as death, transplantation and re-hospitalization for PAH). Drug safety and tolerability were also examined. RESULTS: There were 19 males and 71 females with an average age of 32.5 ± 12.1 years old (range: 18 - 61). Their etiologies were idiopathic (n = 15), related with congenital heart disease (n = 60), or related with connective tissue disease (n = 9) and chronic thromboembolic pulmonary hypertension (n = 6). Oral sildenafil significantly increased the SMWT distances [(342 ± 93) m vs. (403 ± 88) m, P < 0.001]. There was also remarkable improvement in Borg dyspnea score (2.9 ± 2.6 vs. 2.4 ± 2.0, P = 0.005). Furthermore, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also found (mean pulmonary artery pressure, P < 0.001; cardiac index, P < 0.001; pulmonary vascular resistance, P < 0.001). Side effects were mild and consistent with other reports. CONCLUSION: This study confirms and extends previous studies. Oral sildenafil is both safe and effective for the treatment of adult PAH patients in China.

Impact of sildenafil therapy on pulmonary arterial hypertension in adults with congenital heart disease.

BACKGROUND: It has been demonstrated that sildenafil is effective in patients with pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH in adults with congenital heart disease (CHD) has been less investigated. OBJECTIVE: In this prospective, open-label, uncontrolled and multicenter study, 60 patients with PAH related to CHD received oral sildenafil (75 mg/day) for 12 weeks. The enrolled patients underwent six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of the 12 weeks. The primary end point was the changes in exercise capacity assessed by SMWT; the secondary end point included assessment of functional class, evaluation of cardiopulmonary hemodynamics, and clinical worsening (defined as death, transplantation, and rehospitalization for PAH). Drug safety and tolerability were also examined. RESULTS: Oral sidenafil significantly increased SMWT distances (422.94 ± 76.95 m vs. 371.99 ± 78.73 m, P < 0.0001). There was also remarkable improvement in Borg dyspnea score (2.1 ± 1.32 vs. 2.57 ± 1.42, P = 0.0307). Moreover, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also discovered (mean pulmonary artery pressure, P = 0.0002; cardiac index, P < 0.0001; pulmonary vascular resistance, P < 0.0001). Side effects in this study were mild and consistent with reported studies. None of the enrolled patients experienced significant clinical worsening. CONCLUSIONS: This study confirmed and extended previous studies. It suggested that oral sildenafil was safe and effective for the treatment of adult patients with CHD-related PAH.