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Bone metastasis is an essential factor affecting the prognosis of prostate cancer (PCa), and circulating tumor cells (CTCs) are closely related to distant tumor metastasis. Here, the protein-protein interaction (PPI) networks and Cytoscape application were used to identify diagnostic markers for metastatic events in PCa. We screened ten hub genes, eight of which had area under the ROC curve (AUC) values > 0.85. Subsequently, we aim to develop a bone metastasis-related model relying on differentially expressed genes in CTCs for accurate risk stratification. We developed an integrative program based on machine learning algorithm combinations to construct reliable bone metastasis-related genes prognostic index (BMGPI). On the basis of BMGPI, we carefully evaluated the prognostic outcomes, functional status, tumor immune microenvironment, somatic mutation, copy number variation (CNV), response to immunotherapy and drug sensitivity in different subgroups. BMGPI was an independent risk factor for disease-free survival in PCa. The high risk group demonstrated poor survival as well as higher immune scores, higher tumor mutation burden (TMB), more frequent co-occurrence mutation, and worse efficacy of immunotherapy. This study highlights a new prognostic signature, the BMGPI. BMGPI is an independent predictor of prognosis in PCa patients and is closely associated with the immune microenvironment and the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

The balance between the strength and the toughness of pure tantalum (Ta) fabricated with selective laser melting (SLM) additive manufacturing is a major challenge due to the defect generation and affinity for oxygen and nitrogen. This study investigated the effects of energy density and post-vacuum annealing on the relative density and microstructure of SLMed tantalum. The influences of microstructure and impurities on strength and toughness were mainly analyzed. The results indicated that the toughness of SLMed tantalum significantly increased due to a reduction in pore defects and oxygen-nitrogen impurities, with energy density decreasing from 342 J/mm3 to 190 J/mm3. The oxygen impurities mainly stemmed from the gas inclusions of tantalum powders, while nitrogen impurities were mainly from the chemical reaction between the molten liquid tantalum and nitrogen in the atmosphere. The proportion of <110> texture decreased after vacuum-annealing at 1200 °C, while that of the <100> texture increased. Concurrently, the density of dislocations and small-angle grain boundaries significantly decreased while the resistance of the deformation dislocation slip was significantly reduced, enhancing the fractured elongation up to 28% at the expense of 14% tensile strength. [ABSTRACT FROM AUTHOR]

Background: Asthma is a heterogeneous disease with variable symptoms, which presents with cough either as the sole or predominant symptom with or without wheezing. We compared the clinical and pathophysiological characteristics of cough predominant asthma (CPA), cough variant asthma (CVA) and classic asthma (CA) in order to determine any differential phenotypic traits.Methods: In 20 clinics across China, a total of 2088 patients were finally recruited, including 327 CVA, 1041 CPA and 720 CA patients. We recorded cough and wheezing visual analogue scale, Leicester cough questionnaire (LCQ) and asthma control test scores. Fractional exhaled nitric oxide (FeNO), induced sputum cell counts, and capsaicin cough challenge were also measured and compared.Results: CPA patients more frequently presented with cough as the initial symptom, and laryngeal symptoms (p < 0.001), had less symptoms related with rhinitis/sinusitis and gastroesophageal reflux (p < 0.05) than CA patients. Comorbidities including rhinitis and gastroesophageal reflux were similar, while the proportion of COPD and bronchiectasis was higher in CA patients. There were no differences in FeNO levels, sputum eosinophil and neutrophil counts, FEV1 (%pred) decreased from CVA to CPA to CA patients (p < 0.001). Cough sensitivity was higher in CVA and CPA compared to CA (p < 0.001), and was positively correlated with LCQ scores.Conclusions: CVA, CPA and CA can be distinguished by the presence of laryngeal symptoms, cough sensitivity and airflow obstruction. Asthma-associated chronic cough was not associated with airway inflammation or comorbidities in our cohort. Trial registration The Chinese Clinical Trial Registration Center, ChiCTR-POC-17011646, 13 June 2017. [ABSTRACT FROM AUTHOR]

Metformin has been involved in modulating inflammatory state and inhibiting cell proliferation and angiogenesis. This study aimed to determine whether metformin alleviates airway inflammation and remodeling of experimental allergic asthma and elucidate the underlying mechanism. We sensitized and challenged mice with ovalbumin (OVA) to induce allergic asthma. During the challenge period, metformin was administered by intraperitoneal injection. By histopathological and immunohistochemical analyses, metformin-treated mice showed a significant alleviation in airway inflammation, and in the parameters of airway remodeling including goblet cell hyperplasia, collagen deposition and airway smooth muscle hypertrophy compared to those in the OVA-challenged mice. We also observed elevated levels of multiple cytokines (IL-4, IL-5, IL-13, TNF-α, TGF- β 1 and MMP-9) in the bronchoalveolar lavage fluid, OVA-specific IgE in the serum and angiogenesis-related factors (VEGF, SDF-1 and CXCR4) in the plasma from asthmatic mice, while metformin reduced all these parameters. Additionally, the activity of 5′-adenosine monophosphate-activated protein kinase a (AMPK α) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p -AMPK α to AMPK α was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed. These results indicate that metformin ameliorates airway inflammation and remodeling in an OVA-induced chronic asthmatic model and its protective role could be associated with the restoration of AMPK α activity and decreased asthma-related angiogenesis. [ABSTRACT FROM AUTHOR]

Metformin has been involved in modulating inflammatory state and inhibiting cell proliferation and angiogenesis. This study aimed to determine whether metformin alleviates airway inflammation and remodeling of experimental allergic asthma and elucidate the underlying mechanism. We sensitized and challenged mice with ovalbumin (OVA) to induce allergic asthma. During the challenge period, metformin was administered by intraperitoneal injection. By histopathological and immunohistochemical analyses, metformin-treated mice showed a significant alleviation in airway inflammation, and in the parameters of airway remodeling including goblet cell hyperplasia, collagen deposition and airway smooth muscle hypertrophy compared to those in the OVA-challenged mice. We also observed elevated levels of multiple cytokines (IL-4, IL-5, IL-13, TNF-α, TGF- β 1 and MMP-9) in the bronchoalveolar lavage fluid, OVA-specific IgE in the serum and angiogenesis-related factors (VEGF, SDF-1 and CXCR4) in the plasma from asthmatic mice, while metformin reduced all these parameters. Additionally, the activity of 5′-adenosine monophosphate-activated protein kinase a (AMPK α) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p -AMPK α to AMPK α was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed. These results indicate that metformin ameliorates airway inflammation and remodeling in an OVA-induced chronic asthmatic model and its protective role could be associated with the restoration of AMPK α activity and decreased asthma-related angiogenesis. [ABSTRACT FROM AUTHOR]

Metformin has been involved in modulating inflammatory state and inhibiting cell proliferation and angiogenesis. This study aimed to determine whether metformin alleviates airway inflammation and remodeling of experimental allergic asthma and elucidate the underlying mechanism. We sensitized and challenged mice with ovalbumin (OVA) to induce allergic asthma. During the challenge period, metformin was administered by intraperitoneal injection. By histopathological and immunohistochemical analyses, metformin-treated mice showed a significant alleviation in airway inflammation, and in the parameters of airway remodeling including goblet cell hyperplasia, collagen deposition and airway smooth muscle hypertrophy compared to those in the OVA-challenged mice. We also observed elevated levels of multiple cytokines (IL-4, IL-5, IL-13, TNF-α, TGF- β 1 and MMP-9) in the bronchoalveolar lavage fluid, OVA-specific IgE in the serum and angiogenesis-related factors (VEGF, SDF-1 and CXCR4) in the plasma from asthmatic mice, while metformin reduced all these parameters. Additionally, the activity of 5′-adenosine monophosphate-activated protein kinase a (AMPK α) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p -AMPK α to AMPK α was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed. These results indicate that metformin ameliorates airway inflammation and remodeling in an OVA-induced chronic asthmatic model and its protective role could be associated with the restoration of AMPK α activity and decreased asthma-related angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Asthmatic patients with chest tightness as their only presenting symptom (chest tightness variant asthma [CTVA]) have clinical characteristics of eosinophilic airway inflammation similar to those of classic asthma (CA); however, whether CTVA has similar response to antiasthma treatment as compared with CA remains unclear. Objective: The response of 76 CTVA patients to standard asthma treatments with inhaled corticosteroids with long‐acting beta‐agonists was explored in a 52‐week multicenter, prospective, real‐world study. Results: After 52 weeks of treatment with therapy regimens used for CA, the mean 5‐point Asthma Control Questionnaire (ACQ‐5) score decreased markedly from 1.38(first administration) to 0.71 (52 weeks, mean decrease: 0.674, 95%CI: 0.447‐0.900, P<.001).The mean asthma quality‐of‐life questionnaire (AQLQ) score increased from 5.77 (first administration) to 6.20 (52 weeks, mean increase: 0.441, 95% CI 0.258‐0.625, P<.001). Furthermore, at week 52, FVC, FEV1%, the diurnal variation in PEFand the PD20‐FEV1 were significantly improved. Subgroup analysis revealed that the patients at first administration in the responsive group had higher ACQ‐5 scores than those in the nonresponsive group (P <.05). Conclusion: In conclusion, patients with CTVA had a good therapeutic response to the guideline‐recommended routine treatment (containing inhaled corticosteroids). The association between the treatment response and the severity of CTVA suggested that CTVA patients with higher ACQ‐5 scores had better therapeutic effects. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims:Klebsiella pneumoniae represents the most common opportunistic pathogen contributing to Klebsiella pneumonia in hospital-acquired infections. Klebsiella pneumonia has a rapidly progressive clinical course and multi-drug resistant (MDR). Identification of the effective biochemical markers is crucial for improving early diagnosis and treatment of Klebsiella pneumonia. The aims of our study are to 1) investigate the expression of β-Defensin-2(rβD2), IL-22, IL-22R1 and IL-10R2 in Klebsiella pneumonia-infected rats and 2) their association with the histological grades of Klebsiella pneumonia. Methods and Materials: Fifty specific pathogen free (SPF) male SD rats were randomly divided into two groups: control group (treated with normal saline) and pneumonia group (treated with K. pneumoniae). All animals were sacrificed 1 h, 12 h, 1 d, 3 d, 5 d post infection. The severity and property of pneumonia was evaluated by histopathologic observation and pathogen identification. The mRNA expression of rβD2, IL-22, IL-22R1 and IL-10R2 was measured by RT-qPCR assay. The expression of rβD2 in rat lung tissue was determined by Western blot analysis, and the level of IL-22 in rat serum was determined by ELISA. Results: Histopathologic examination and bacterial counting of lung tissues confirmed the successful establishment of rat pneumonia model. The gene expression of rβD2, IL-22, IL-22R1 and IL-10R2 in pneumonia rats were significantly higher than those in healthy control mice (P < 0.05). The expression of rβD2 was correlated with histological grades of Klebsiella pneumonia and the level of IL-22. RT-qPCR results showed that the peak expression of IL-22R1 appeared earlier than IL-10R2 in rat pneumonia model. Conclusions: The expression of rβD2 and IL-22 was increased significantly at early stage in rat Klebsiella pneumonia model, suggesting that IL-22 and rβD2 might serve as potential biomarkers for the early diagnosis of Klebsiella pneumonia. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the aging of the population, the incidence of distal radius fracture is gradually increasing. Non-operative external fixation splint can reduce the economic burden, mental burden and prevent surgical trauma. Therefore, the study of external fixation splint for distal radius fracture has important clinical value and significance. OBJECTIVE: To summarize the research status of distal radius fracture fixation splints and to lay a foundation for further research. METHODS: The first author searched the CNKI, Wanfang and VIP database, PubMed, Embase and Web of Knowledge for studies regarding external fixation splint for distal radius fracture published from 2000 to 2019. The key words were "distal radius fracture, external fixation, splint" in Chinese and English. RESULTS AND CONCLUSION: (1) The improved design of the shape, material and fixation band of the traditional small splint is the key direction of splint research at present. The improved design of splint shows great advantages in clinical application. (2) With the advancement of social science and technology, the emergence of new materials, new technologies and the deepening of biomechanical research, distal radius fracture fixation splint integrated with the elements of modem science and technology is the development trend of small splint in the future. [ABSTRACT FROM AUTHOR]

Abstract: A mixed‐lubrication numerical model for hydraulic seals by the inverse‐hydrodynamic‐lubrication method is presented in this paper for the first time. The hydrodynamic effect on the seal inlet is taken into account as well as the asperity contact pressures. The coupling relationship between the fluid pressure, asperity contact pressure, and static contact pressure is provided by finite‐element analysis. The reverse pumping rate and friction force are calculated from the model under different fluid‐pressure and rod‐velocity conditions. All calculation results agree well with the experimental results, which are measured by the bench test as developed by the authors. By this new model, the average relative error between calculation results and experimental results is 10.5% under all test conditions, compared with 62.6% of the results by full‐film lubrication model. [ABSTRACT FROM AUTHOR]

Objectives: Understanding the interactions between allergic rhinitis (AR) and asthma is important for asthma management. This study explored the clinical features of AR as a comorbidity in Chinese asthmatic patients and its impact on asthma control. Methods: This cross-sectional survey was conducted among 20 051 patients with asthma in an out-patient setting and covered all of the territories of China. The patients were interviewed face-to-face. A standardized questionnaire was completed by each patient. AR was defined according to the ARIA criteria. The level of asthma control was assessed by the Asthma Control Test. A score ≤19 indicated poorly controlled asthma. Results: AR was present in 69.9% of patients with asthma. Of them, 72.4% had intermittent symptoms, and 93.1% presented with moderate/severe symptoms. Cold air, irritant air and household mites were the most common triggers for AR. A higher percentage of patients with AR experienced poorly controlled asthma compared with those without AR (56.2% versus 51.5%, p < 0.001). AR was associated with an increased risk of poorly controlled asthma [odds ratio (OR): 1.21, p < 0.001]. Moderate/severe or persistent symptoms were associated with a higher risk of poorly controlled asthma than those with mild or intermittent symptoms (OR: 2.34 and 1.78, respectively, p < 0.001). In contrast, diagnosed AR (OR: 0.84, p < 0.001), being currently treated with medication (OR: 0.91, p = 0.004) and a prior skin prick test (OR: 0.90, p = 0.003) showed a significantly negative association with poorly controlled asthma. Conclusion: This study confirms that concomitant AR and asthma are highly prevalent in China and that AR is associated with poor asthma control. [ABSTRACT FROM AUTHOR]

Background and objective This study, in a predominantly Chinese population, investigated the efficacy and safety of a once-daily (o.d.) inhaled ultra-long-acting β2-agonist indacaterol for the treatment of moderate-to-severe chronic obstructive pulmonary disease ( COPD). Methods This is a 26-week, double-blind study on randomized patients who received indacaterol 150 μg or 300 μg or placebo o.d. The primary variable was trough forced expiratory volume in 1 s ( FEV1, average of 23 h 10 min and 23 h 45 min post-dose values) at Week 12. Health status ( St George's Respiratory Questionnaire, SGRQ), dyspnoea (transition dyspnoea index, TDI) and safety were evaluated over 26 weeks. Results Of the 563 patients randomized, 561 (89.8% Chinese) received treatment and 482 completed. At Week 12, trough FEV1 improved significantly for indacaterol 150 and 300 μg versus placebo (1.32, 1.29 vs 1.17; P < 0.001 for both comparisons), with differences exceeding the pre-specified minimal clinically important difference of 0.12 L. At Week 26, TDI score was superior to placebo for indacaterol 150 and 300 μg (0.82, 1.15; P < 0.01), as was the percentage of patients with a clinically relevant improvement (≥1 point) (74.1%, 78.6% vs 55.5%; P < 0.05). Both doses provided ≥4-point improvements from baseline in SGRQ score at Week 26 that were numerically greater than placebo (unadjusted means: −9.6, −8.8 vs −7.0), with a similar pattern in percentage of patients with clinically relevant improvements in SGRQ score (65.0%, 61.5% vs 60.6%). Incidences of adverse events were comparable across treatment groups. Conclusions Indacaterol delivered effective bronchodilation with significant improvements in breathlessness and health status in this predominantly Chinese population. [ABSTRACT FROM AUTHOR]

Asthma, airway inflammation, airway remodeling, metformin, AMPK Corrigendum: Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPK Activity Keywords: asthma; airway inflammation; airway remodeling; metformin; AMPK EN asthma airway inflammation airway remodeling metformin AMPK 1 1 1 04/26/22 20220421 NES 220421 In the published article, there was an error regarding the affiliation for "Changgui Wu". [Extracted from the article]

Background: Little is known about asthma control and perception of asthma among asthmatic patients on a national scale in China due to the difficulty of conducting a survey of the large, vastly distributed population of the country. We know that the medical insurance system may not evenly cover all patients and that socioeconomic status varies greatly across cities. Objective: This study marks the first survey conducted on a national scale that was aimed at obtaining baseline information on asthma control and patients' perceptions of asthma and providing a point of reference for future studies. Methods: This face-to-face, questionnaire-based survey was conducted from April 2007 to March 2008 in 3069 asthmatic patients from the respiratory outpatient clinics of 36 general hospitals located in 10 geographically dispersed cities. Results: Per the Global Initiative for Asthma (GINA) guidelines, 28.7% and 45.0% of our patients achieved complete or partial asthma control, respectively. Of patients in the study, only 21.8% had used a peak flow meter (PFM) and 6.6% of these patients used it daily. Inhaled corticosteroids (ICS) plus a long-acting β2 agonist and ICS were the two most common medication regimens and were used in 45.6% and 30.4% of patients, respectively. Asthma had a significant effect on patients' life and work. A considerable number of hospitalizations, emergency department visits and sick days were also observed. Conclusions: Despite improvements in asthma control and ICS and PFM compliance compared with past literature, the current level of asthma control countrywide continues to fall short of the goals set in the GINA. [ABSTRACT FROM AUTHOR]

Objectives. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has immune- and inflammation-modulating properties in asthma, but its possible effects on asthmatic airway remodeling remain uncertain. In this study, we investigated the effects of 1,25-(OH)2D3 on airway remodeling in a murine model of chronic asthma and investigated its role in regulating nuclear factor- κB (NF- κB) activation. Methods. BALB/c mice were sensitized to ovalbumin (OVA) and subsequently exposed to intranasal OVA challenges for 9 weeks. Some mice also received an intraperitoneal injection of 1,25-(OH)2D3 at the time of challenge. At the end of the challenge period, mice were evaluated for chronic airway inflammation and airway remodeling. Nuclear translocation of NF- κB p65 in lung tissue was examined by Western blot. Inhibitor of NF- κB alpha (I κB α) expression was determined by real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot. Phosphorylated I κB α protein expression was also determined by Western blot. Results. 1,25-(OH)2D3 treatment reduced OVA-induced chronic inflammation in lung tissue and attenuated established structural changes of the airways, including subepithelial collagen deposition, goblet cell hyperplasia, and increased airway smooth muscle mass. 1,25-(OH)2D3 also inhibited the nuclear translocation of NF- κB p65 in lung tissue. Concurrently, 1,25-(OH)2D3 induced increased I κB α protein levels via inducing increased I κB α mRNA levels and decreased I κBα phosphorylation. Conclusion. 1,25-(OH)2D3 could attenuate asthmatic airway remodeling and its inhibition of NF- κB activation may underlie this protective effect. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to assess the efficacy, safety and tolerability of oral moxifloxacin in patients with respiratory tract infections (RTIs) treated by attending physicians in routine clinical practice in China. METHODS: This was an open-label, prospective, uncontrolled, post-marketing surveillance study that was undertaken between November 2002 and July 2003. Altogether, 855 patients with RTIs were treated with moxifloxacin. Data were collected by 257 physicians throughout China. Symptoms of RTI (fever, cough, purulent sputum, dyspnoea, thoracic pain, nasal obstruction, nasal secretion and headache), together with auscultatory findings, were assessed at baseline and at follow-up visits, and classified as ‘absent’, ‘mild’ or ‘severe’ by the attending physician. RESULTS: Moxifloxacin produced significant improvements in 70.7% of patients after only 3 days of treatment. In 91.7% of patients, symptoms were improved after 5 days of treatment; 76.1% of patients recovered after 7 days and 84.7% recovered after 10 days of treatment. The mean ± SD time until recovery was 5.1 ± 2.6 days. Assessment of treatment efficacy by the physicians was ‘good’ or ‘very good’ for 89.2% of patients. In 87.3% of cases, physicians rated patients’ acceptance of therapy with moxifloxacin as ‘good’ or ‘very good’. The tolerability of moxifloxacin therapy was rated as ‘good’ or ‘very good’ for 88.8% of patients. Very few adverse events (4.1% of patients) were reported with moxifloxacin; most of them involved mild CNS disorders and gastrointestinal disturbances. CONCLUSIONS: Moxifloxacin was shown to be an effective and well tolerated treatment for this group of patients with RTIs and was highly rated by both physicians and patients because of rapid symptom improvement and good tolerability. [ABSTRACT FROM AUTHOR]

Background:Asthma is a complex and heterogeneous chronic inflammatory disorder that is associated with mucous cell metaplasia and mucus hypersecretion. Functional genomic analysis indicates that mucous cell metaplasia and mucus hypersecretion depend on members of the calcium-activated chloride channel (CLCA) gene family. It has been reported that the inhibition of CLCAs could relieve the symptoms of asthma. Thus, the mCLCA3 antibody may be a promising strategy to treat allergic diseases such as asthma. Methods:We constructed asthmatic mouse models of OVA-induced chronic airway inflammatory disorder to study the function of the mCLCA3 antibody. Airway inflammation was measured by HE staining; goblet cell hyperplasia and mucus hypersecretion were detected by PAS staining; muc5ac, IL-13, IFN-γ levels in bronchoalveolar lavage fluid (BALF) were examined by ELISA; Goblet cell apoptosis was measured by TUNEL assay and alcian blue staining; mCLCA3, Bcl-2 and Bax expression were detected by RT-PCR, Western blotting and immunohistochemical analysis. Results:In our study, mice treated with mCLCA3 antibody developed fewer pathological changes compared with control mice and asthmatic mice, including a remarkable reduction in airway inflammation, the number of goblet cells and mCLCA3 expression in lung tissue. The levels of muc5ac and IL-13 were significantly reduced in BALF. We also found that the rate of goblet cell apoptosis was increased after treatment with mCLCA3 antibody, which was accompanied by an increase in Bax levels and a decrease in Bcl-2 expression in goblet cells. Conclusions:Taken together, our results indicate that mCLCA3 antibody may have the potential as an effective pharmacotherapy for asthma. [ABSTRACT FROM AUTHOR]