Characteristics of different asthma phenotypes associated with cough: a prospective, multicenter survey in China.

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.

Disruption of the Notch pathway aggravates airway inflammation by inhibiting regulatory T cell differentiation via regulation of plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) regulate immunity and promote tolerance in asthma. Notch signalling is a highly conserved pathway that regulates the immune response; however, its role in pDC-mediated asthmatic airway inflammation is unclear. This study clarified the effects of Notch signalling on pDC-mediated airway inflammation using murine models of ovalbumin-sensitized allergic asthma. RBP-J-deficient pDCs (RBP-J-/- pDCs) were co-cultured with naïve CD4+ T cells and supernatants and T cell subtypes were analysed. RBP-J-/- pDCs were intranasally transferred to the airways of ovalbumin-sensitized recipient mice. Lung samples of all mice were subjected to tests for histopathology, cytokine profile of bronchoalveolar lavage fluid, airway hyperactivity and expression of T helper type 1 (Th1)/Th2 cells, regulatory T cells and type 2 innate lymphoid cells (ILC2s). The results showed that pDCs with and without RBP-J deficiency significantly differed in expression levels of cluster of differentiation 83 (CD83), but not CD80, CD86 and major histocompatibility complex class II. Co-culturing pDCs with naïve T cells revealed a poorer immunosuppressive effect of RBP-J-/- pDCs. This may be attributed to the lower expression levels of inducible co-stimulator ligand and lower production of interleukin 10 in RBP-J-/- pDCs than in control pDCs, which impeded T cell activation and Treg suppression. RBP-J-/- pDCs were associated with high ILC2 expression and severe Th2 immune responses and airway inflammation. Therefore, Notch signalling is critical for pDC-dependent immunoregulation, and RBP-J deficiency reduces pDC-based immunosuppression via T cell activation and Th cell differentiation. Thus, this pathway may be a therapeutic target for pDC-based anti-asthma immunotherapy.

The expression of ß-Defensin-2, IL-22, IL-22R1 and IL-10R2 in rat model of Klebsiella pneumonia and their correlation with histological grades.

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 ß-Defensin-2(rßD2), 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 rßD2, IL-22, IL-22R1 and IL-10R2 was measured by RT-qPCR assay. The expression of rßD2 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 rßD2, 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 rßD2 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 rßD2 and IL-22 was increased significantly at early stage in rat Klebsiella pneumonia model, suggesting that IL-22 and rßD2 might serve as potential biomarkers for the early diagnosis of Klebsiella pneumonia.

Network Pharmacology to Identify the Pharmacological Mechanisms of a Traditional Chinese Medicine Derived from Trachelospermum jasminoides in Patients with Rheumatoid Arthritis.

BACKGROUND This study used a network pharmacology approach to identify the pharmacological mechanisms of a traditional Chinese medicine derived from Trachelospermum jasminoides (Lindl.) Lem. in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS Known compounds of T. jasminoides were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the Shanghai Institute of Organic Chemistry of Chinese Academy of Science, Chemistry (CASC) database, and a literature search. Putative targets of identified compounds were predicted by SwissTargetPrediction. RA-related targets were achieved from the Therapeutic Target database, Drugbank database, Pharmacogenomics Knowledgebase, and Online Mendelian Inheritance in Man database. The protein-protein interaction (PPI) network was built by STRING. CluGO was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis. RESULTS A total of 354 potential targets were predicted for the 17 bioactive compounds in T. jasminoides; 69 of these targets overlapped with RA-related targets. A PPI network was composed and 2 clusters of 59 and 42 nodes each were excavated. GO and KEGG enrichment analysis of the overlapping targets and the 2 clusters was mainly grouped into immunity, inflammation, estrogen, anxiety, and depression processes. CONCLUSIONS Our study illustrated that T. jasminoides alleviates RA through the interleukin-17 signaling pathway, the tumor necrosis factor signaling pathway, and other immune and inflammatory-related processes. It also may exert effects in regulating cell differentiation and potentially has anti-anxiety, anti-depression, and estrogen-like effects.

EPO modified MSCs can inhibit asthmatic airway remodeling in an animal model.

There was no effective measures can be obtained at present to reverse or prevent airway remodeling. We investigated the therapeutic effect of Erythropoietin (EPO) gene modified mesenchymal stem cells (MSCs) on asthmatic airway remodeling and the possible underlied molecular mechanisms. EPO gene was transfected into MSCs via lentivirus vector. The transfected cells (EPO-MSCs) were identified by flow cytometry and the EPO secreting function was detected by PCR and Western blot. MSCs or EPO-MSCs were administrated to albumin (OVA)-induced chronic asthmatic mouse model via tail veins. The asthmatic phenotype was analyzed. Number of cells in bronchoalveolar lavage fluid (BALF) was counted using a hemocytometer. Histological findings of airways were evaluated by microscopic examination. The concentrations of interleukin 4(IL-4), interleukin 5(IL-5), and interleukin 13(IL-13) in lung homogenate were determined by ELISA. The activation state of transforming growth factor-ß 1 (TGF-ß1), Transforming growth factor beta-activated kinase 1 (TAK1), and p38 Mitogen Activated Protein Kinase (p38MAPK) signaling was detected by Real-Time PCR and Western blotting. EPO-MSCs were successfully constructed. EPO-MSCs showed a more potently suppressive effect on local asthmatic airway inflammation and the level of IL-4, IL-5, and IL-13 in lung tissue than MSCs. Moreover, the numbers of goblet cells, the thicknesses of smooth muscle layer, collagen density, percentage of proliferating cell nuclear antigen positive (PCNA+ ) mesenchymal cells, and von Willebrand factor positive(vWF+ ) vessels were also significantly inhibited by EPO-MSCs. Furthermore, EPO-MSCs could downregulate the expression of TGF-ß1, TAK1, and p38MAPK in lung tissue both in mRNA level and in protein level. EPO gene modified MSCs may more efficiently attenuate asthmatic airway remodeling, which maybe related with the downregulation of TGF-ß1-TAK1-p38MAPK pathway activity.

Transcription factor RBP-J-mediated signalling regulates basophil immunoregulatory function in mouse asthma model.

Basophils (BA) play an important role in the promotion of aberrant T helper type 2 (Th2) immune responses in asthma. It is not only the effective cell, but also modulates the initiation of Th2 immune responses. We earlier demonstrated that Notch signalling regulates the biological function of BAin vitro. However, whether this pathway plays the same role in vivo is not clear. The purpose of the present study was to investigate the effect of Notch signalling on BA function in the regulation of allergic airway inflammation in a murine model of asthma. Bone marrow BA were prepared by bone marrow cell culture in the presence of recombinant interleukin-3 (rIL-3; 300 pg/ml) for 7 days, followed by isolation of the CD49b+ microbeads. The recombination signal binding protein J (RBP-J-/- ) BA were co-cultured with T cells, and the supernatant and the T-cell subtypes were examined. The results indicated disruption of the capacity of BA for antigen presentation alongside an up-regulation of the immunoregulatory function. This was possibly due to the low expression of OX40L in the RBP-J-/- BA. Basophils were adoptively transferred to ovalbumin-sensitized recipient mice, to establish an asthma model. Lung pathology, cytokine profiles of brobchoalveolar fluid, airway hyperactivity and the absolute number of Th1/Th2 cells in lungs were determined. Overall, our results indicate that the RBP-J-mediated Notch signalling is critical for BA-dependent immunoregulation. Deficiency of RBP-J influences the immunoregulatory functions of BA, which include activation of T cells and their differentiation into T helper cell subtypes. The Notch signalling pathway is a potential therapeutic target for BA-based immunotherapy against asthma.

Notch signaling pathway regulates the growth and the expression of inflammatory cytokines in mouse basophils.

Basophils (BAs) are the least common granulocytes of all leukocytes, but they play an important role in orchestrating of chronic allergic inflammation. The Notch signaling pathway is a highly conserved pathway that influences cell lineage decisions and differentiation during various stages of development. However, the relationship between Notch signaling and BA remains to be elucidate. Here, we report that several Notch signaling molecules were found to be expressed in BAs. γ-secretase inhibitor (GSI) treatment increase BAs apoptosis, and suppress BAs proliferation. Furthermore, GSI reduced BAs in the S phase, with a concomitant accumulation in G1 and G2 phases. In addition, GSI also significantly down-regulated mRNA levels of cytokines IL-4, IL-6 and IL-13 induced by A23187, and this effect was dependent on MAPK pathway. Finally, IL-6 inhibition was specifically associated with ERK and IL-13 with JNK. Therefore, Notch signaling regulates BA biological function, at least partially via the modulation of MAPK.

Association of the glucocorticoid receptor D641V variant with steroid-resistant asthma: a case-control study.

OBJECTIVES: Several mutations of the glucocorticoid receptor (GR) gene cause malfunction of the protein, resulting in steroid resistance. In diseases other than asthma, the GR variants I559N, D641V, and V729I have been linked to steroid resistance. The aim of this study was to evaluate the link of these GR variants in steroid-resistant (SR) asthma in the Chinese Han population. METHODS: GR polymorphisms were determined in 64 SR asthma patients, 217 steroid-sensitive (SS) asthma patients and 221 healthy control (CTR) individuals. The analysis of the GR variants was performed using PCR-sequence specific primers according to the European Molecular Biology Laboratory database (NC_000005.8). In addition, ligand binding and serum cortisol levels were determined. RESULTS: Compared with SS asthma patients and CTRs, a significant lower frequency of the GR D641V variant AA genotype (P=0.003, 0.014, respectively) and the A allele (P=0.001, 0.009, respectively) was found in SR asthma patients. Furthermore, the equilibrium dissociation constant (Kd) of GR ligand binding in SR asthma patients with the GR D641V variant AA genotype was significantly lower compared with the AT or the TT genotype carriers (P=0.006, 0.016, respectively). There was no significant difference between the I559N and V729I GR variants on comparing SR asthma patients with SS asthma patients or CTRs. CONCLUSION: This study suggests that the D641V variant of the GR is probably associated with SR asthma in the Chinese Han population.

[An epidemiological survey on management and insights of asthma in China in 2009 to 2010].

OBJECTIVE: Through the analysis of relevant data of China Asthma and Risk factors Epidemiologic investigation (CARE study), we understand the status quo of management and insights of asthma patients in our country. METHODS: Using multi-stage random cluster sampling method, epidemiological survey was performed on the prevalence rate in 8 provinces (cities) of China residents who aged over 14 years from 2009 to 2010. Detailed epidemiological data was collected via face-to-face home visit interview among 2 034 asthmatics who were diagnosed in the last epidemiology survey. Asthma was diagnosed based upon case history, clinical signs and lung function test. The SPSS12.0 software was conducted for statistical analysis and the status of asthma control was investigated. RESULTS: This survey has shown that 22.71% (462/2 034) asthmatics had ever taken a lung functional test in the past year. A total of 294 (14.45%) people had peak flow meters but only 1.62% (33/2 034) regularly used it daily. There were 22.42% (456/2 034) asthmatics aware that bronchial asthma is characterized by chronic airway inflammation. 14.85% (302/2 034) asthmatics understood that the treatment goal of this disease is long-term good control or complete control. This survey has found that 59.64% (1 213/2 034) patients complained that asthma has affected their work, life and entertainment, including 8.90% (181/2 034) asthmatics dependent on instruments in daily life and 4.57% attempting to suicide. This suggested that allergic asthma has seriously decreased the quality of life. CONCLUSION: Therefore it is necessary to educate the asthmatics, guide the patients to the long-term management and standardized therapy and raise the level of disease understanding, thus reducing the burden of disease to society. Gaining better insight of patient's attitude about self-care is critical to the improvement of asthma management.

[Efficacy and Safety of Tiotropium Bromide in the Treatment of Chronic Obstructive Pulmonary Disease--a Multi-center Randomized Clinical Trial].

OBJECTIVE: To investigate the efficacy and safety of domestic tiotropium inhalation capsule in patients with chronic obstructive pulmonary disease (COPD) with multi-center randomized clinical trial. METHODS: Patients with stable slight to moderate COPD were randomized into trial group (n=109) with tiotropium 18 pg Qd or control group (n =111) with ipratropium 40 µg Qid for a treatment of four weeks. The spirometry and scoring questionaire were recorded at different visits during the treatment. Rescue medication consumption and adverse events were recorded. Results Forced expiratory volume in 1 s (FEV1) of both groups increased obviously 30 min and 3 h after first dosing. After four weeks treatments, FEV, and forced vital capacity (FVC) in both groups were improved obviously, and the improvement in tiotropium group was significantly higher than that ipratropium group. COPD symptom scores were significantly reduced in both groups, and the improvement in tiotropium group was significantly better than that in ipratropium group. There was no significant difference in rescue medication consumption between the two groups. The ratios of adverse events were 22. 02% and 15. 32% in tiotropium and ipratropium group, respectively (P=0. 23). CONCLUSION: Domestic tiotropium inhalation capsule is efficient and safe in the treatment of COPD.

DW MRI at 3.0 T versus FDG PET/CT for detection of malignant pulmonary tumors.

Emerging evidence suggests that diffusion-weighted magnetic resonance imaging (DW MRI) could be useful for tumor detection with N and M staging of lung cancer in place of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). DW MRI at 3.0 T and FDG PET/CT were performed before therapy in 113 patients with pulmonary nodules. Mean apparent diffusion coefficient (ADC), maximal standardized uptake value (SUVmax ) and Ki-67 scores were assessed. Quantitatively, specificity and accuracy of ADC (91.7 and 92.9%, respectively) were significantly higher than those of SUVmax (66.7 and 77.9% respectively, p < 0.05), although sensitivity was not significantly different between them (93.5 and 83.1%, p > 0.05). Qualitatively, sensitivity, specificity and accuracy of DW MRI (96.1, 83.3 and 92.0%, respectively) were also not significantly different from that of FDG PET/CT (88.3, 83.3 and 86.7%, respectively, p > 0.05). Significant negative correlation was found between Ki-67 score and ADC (r = -0.66, p < 0.05), ADC and SUVmax (r = -0.37, p < 0.05), but not between Ki-67 score and SUVmax (r = -0.11, p > 0.05). In conclusion, quantitative and qualitative assessments for detection of malignant pulmonary tumors with DW MRI at 3.0 T are superior to those with FDG PET/CT. Furthermore, ADC could predict the malignancy of lung cancer.

The impact of concomitant allergic rhinitis on asthma control: a cross-sectional nationwide survey in China.

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.

Der p2 recombinant bacille Calmette-Guerin priming of bone marrow-derived dendritic cells suppresses Der p2-induced T helper17 function in a mouse model of asthma.

BACKGROUND AND OBJECTIVE: Previous studies have demonstrated that our recombinant bacille Calmette-Guerin (rBCG), which expresses Der p2 in house dust mite (Der p2 rBCG) suppresses asthmatic airway inflammation by regulating the phenotype and function of dendritic cells (DC) and reprogramming T helper (Th) 0 cell differentiation into different T cell (Th1/Th2/Treg) subtypes. However, the exact role of Der p2 rBCG in reprogramming Th17 differentiation and the relevant mechanisms are not known. The aim of this study was to examine whether Der p2 rBCG-mediated inhibition of allergic airway inflammation is mediated by regulating Th17 differentiation in a murine asthma model. METHODS: Primary mouse bone marrow-derived dendritic cells (BMDC) were infected with Der p2 rBCG and adoptively transferred to Der p2-intranasally sensitized mice. The role of Der p2 rBCG-BMDC on the regulation of airway inflammation and Th17 cell differentiation was assessed. RESULTS: Adoptive transfer of Der p2 rBCG-BMDC suppressed airway inflammation and mucin secretion. Der p2 rBCG-BMDC inhibited excessive Th17 immune responses but not BCG-BMDC. Furthermore, Der p2 rBCG decreased jagged-2 and increased delta-like-4 expressions on BMDC to a greater extent than BCG. CONCLUSIONS: These findings suggest that DC plays a key role in Der p2 rBCG-induced immunoregulation. Der p2 rBCG also displayed a potent inhibitory effect on Th17 differentiation, and these findings increase our understanding of the cellular basis of Der p2 BCG-mediated inhibition of asthma.

Effect of once-daily indacaterol in a predominantly Chinese population with chronic obstructive pulmonary disease: a 26-week Asia-Pacific study.

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 ß2 -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.

[An epidemiological survey of current asthma control status in China].

OBJECTIVE: Base on the China asthma and risk factors epidemiologic investigation (CARE study), we analyzed the current status of asthma control in China. METHODS: With the multi-stage random cluster sampling method, epidemiological survey was performed among Chinese residents who aged over 14 years in 8 provinces (cities) from 2010 to 2011. Detailed clinic data of 2 034 asthma patients were collected via face-to-face home visit . Asthma was diagnosed based upon the history, clinical signs and lung function tests. The SPSS 12.0 was conducted for statistics analysis. RESULTS: This survey found that the prevalence rate of asthma in China was 1.24% (2 034/164 215), including 973 male and 1 061 female patients, with a mean age of (56 ± 18) years old. Consistent with the Global Initiative for Asthma (GINA) guidelines, 40.51% (824/2 034) and 42.58% (866/2 034) of our patients achieved control and partial control, respectively. According to the asthma control test (ACT) estimates, 15.63% (318/2 034) and 49.46% (1 006/2 034) of patients achieved full control (ACT 25) and well control(ACT 20-24), respectively. In the past year, 22.62% (460/2 034) of patients reported hospitalized and 26.99% (549/2 034) of patients reported emergency room visit at least one time due to asthma exacerbation. 61.80% (1 257/2 034) of patients were on daily us of medication. Inhaled corticosteroids (ICS) plus a long-acting ß2 agonist (LABA) or solely ICS were used in 6.39% and 14.75% of patients, respectively. Theophylline treatment accounted for 29.11% (592/2 034). Oral glucocorticoid and oral leukotriene modifier (LTRA) treatment accounted for 9.49% (193/2 034) and 3.10% (63/2 034), respectively. According to the survey, 34.51% (702/2 034) of asthma patients reported a history of smoking . The percentage of asthma control in non smoking patients was higher than in smoking patients [43.24% (576/1 332) and 35.33% (248/702), respectively]. Meanwhile, the rates of both hospitalization and emergency due to asthma exacerbation in smoking asthma patients were significantly higher than nonsmoking asthma patients (27.35% and 31.77%, 20.12% and 24.47%, respectively). CONCLUSIONS: The situation of asthma control has been improved in China. However, compared with GINA guidelines, there is still a considerable gap. Smoking is one of the crucial factors that affect asthma control.

[Risk factors of bronchial asthma among people aged over 14 years in China].

OBJECTIVE: To survey the risk factors of asthma among the people aged over 14 years in China. METHODS: Home visits for completing epidemiological questionnaires in accordance with stratified cluster random sampling survey were conducted in 8 provinces (cities) of China residents aged over 14 years from February 2010 to August 2011. Asthma was diagnosed based upon case history, clinical signs and lung function test. The SPSS 12.0 software was used for statistic analyses for the epidemiological status of asthma. RESULTS: Sampling population was composed of 180 099 subjects. Among 164 215 valid questionnaires, there were 79 692 males and 84 523 females, 2 034 had asthma. The overall prevalence rate was 1.2% (2 034/164 215). Correlation analyses showed that the risk factors were smoking (OR = 1.697, 95%CI: 1.547-1.861), breast feeding (OR = 0.801, 95%CI: 0.670-0.959), genetics (OR & 95%CI >1, asthma (OR = 10.440, 95%CI: 8.991-12.112)), complications (OR & 95%CI >1), body mass index (compared with normal weight, overweight (OR = 1.360, 95%CI: 1.212-1.531), obesity (OR = 10.631, 95%CI: 9.570-11.801)) and petting (OR & 95%CI >1). CONCLUSION: Among Chinese asthmatics aged over 14, their risk factors include host (genetics & obesity) and environmental (smoking, breastfeeding, complications & pets) factors.

Mendelian randomization reveals the impact of diet on infertility in men and women.

Background: Although studies on the effects of diet on fertility has progressed, some cumulative evidence has piled against popular hypotheses. The aim of our study was to investigate the effects of 31 diets including 23 individual dietary intakes and 8 dietary habits on infertility in men and women. Methods: The datas of diets and infertility were collected from genome-wide association studies (GWAS). Mendelian randomization (MR) methods were used to analyze causal relationships. Multivariate MR (MVMR) adjusted for the effects of other exposures on causality. And MR-Egger, Cochran's Q, radial MR, and MR-PRESSO tests were employed to assess heterogeneity and horizontal pleiotropy. Results: Our study found that coffee intake (OR, 3.6967; 95% CI, 1.0348 - 13.2065; P = 0.0442) and cooked vegetable intakes (OR, 54.7865; 95% CI, 2.9011 - 1030.5500; P = 0.0076) increased the risk of male infertility. For women, beer was a risk factor for infertility (OR, 4.0932; 95% CI, 1.8728 - 8.9461; P = 0.0004); but processed meat was negatively associated with infertility (OR, 0.5148; 95% CI, 0.2730 - 0.9705; P = 0.0401). MVMR demonstrated selenium as a protective factor against female infertility (OR, 7.4474e-12; 95% CI, 5.4780e-22 - 1.0125e-01; P = 0.0314). Conclusion: We found the causal relationships between four diets and infertility. We look forward to more high-quality epidemiologic studies to prove our conclusions.

Integrated machine learning algorithms reveal a bone metastasis-related signature of circulating tumor cells in prostate cancer.

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.

Efficacy and toxicity of immune checkpoint inhibitors combination therapy for advanced renal cell carcinoma: a systematic review and network meta-analysis.

Background: Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response to these agents remains poor. Some studies have shown that combination therapy including an ICI appears to be the best treatment; however, the overall benefit in terms of efficacy and toxicity still needs to be assessed. Thus, we performed a network meta-analysis to evaluate the differences in the efficacy of several combinations that include an ICI to provide a basis for clinical treatment selection. Methods: We conducted a thorough search of PubMed, EMBASE, and the Cochrane Library for articles from January 2010 to June 2023. R 4.4.2 and STATA 16.0 were used to analyze data; hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to assess the results. Results: An indirect comparison showed that nivolumab plus cabozantinib and pembrolizumab plus lenvatinib were the most effective treatments for progression-free survival (PFS), with no significant differences between the two interventions (HR, 1.31; 95% CI, 0.96-1.78; P=0.08); rank probability showed that pembrolizumab plus lenvatinib had a 57.1% chance of being the preferred treatment. In the absence of indirect comparisons between pembrolizumab plus axitinib, nivolumab plus ipilimumab, avelumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib, pembrolizumab plus axitinib (40.2%) was the best treatment option for overall survival (OS). Compared to pembrolizumab plus lenvatinib, nivolumab plus ipilimumab (OR, 0.07; 95% CI, 0.01-0.65; P=0.02) and pembrolizumab plus axitinib (OR, 0.05; 95% CI, 0.00-0.78; P<0.001) had a lower incidence of overall adverse events (AEs). Conclusion: Pembrolizumab plus lenvatinib and pembrolizumab plus axitinib resulted in the highest PFS and OS rates, respectively. Pembrolizumab plus axitinib may be the best option when AEs are a concern. Systematic review registration: https://inplasy.com/, identifier INPLASY202410078.

Topology-Optimized Splints vs Casts for Distal Radius Fractures: A Randomized Clinical Trial.

Importance: To date, there is currently no evidence-based medical support for the efficacy of topology-optimized splints in treating distal radius fractures. Objective: To assess the clinical efficacy and complication rates of topology-optimized splints in the treatment of distal radius fractures after closed manual reduction. Design, Setting, and Participants: This 12-week, multicenter, open-label, analyst-blinded randomized clinical trial (comprising a 6-week intervention followed by a 6-week observational phase) was carried out from December 3, 2021, to March 10, 2023, among 110 participants with distal radius fractures. Statistical analysis was performed on an intention-to-treat basis between June 3 and 30, 2023. Intervention: Participants were randomly assigned to 2 groups: the intervention group received topology-optimized splint immobilization and the control group received cast immobilization after closed manual reduction for 6weeks. After this period, immobilization was removed, and wrist rehabilitation activities commenced. Main Outcomes and Measures: The primary outcome was the Gartland-Werley (G-W) wrist score at 6 weeks (where higher scores indicate more severe wrist dysfunction). Secondary outcomes encompassed radiographic parameters, visual analog scale scores, swelling degree grade, complication rates, and 3 dimensions of G-W wrist scores. Results: A total of 110 patients (mean [SD] age, 64.1 [12.7] years; 89 women [81%]) enrolled in the clinical trial, and complete outcome measurements were obtained for 101 patients (92%). Median G-W scores at 6 weeks were 15 (IQR, 13-18) for the splint group and 17 (IQR, 13-18) for the cast group (mean difference, -2.0 [95% CI, -3.4 to -0.6]; P = .03), indicating a statistically significant advantage for the splint group. At 12 weeks, no clinically significant differences in G-W scores between the 2 groups were observed. Complication rates, including shoulder-elbow pain and dysfunction and skin irritation, were less common in the splint group (shoulder-elbow pain and dysfunction: risk ratio, 0.28 [95% CI, 0.08-0.93]; P = .03; skin irritation: risk ratio, 0.30 [95% CI, 0.10-0.89]; P = .02). Conclusions and Relevance: Findings of this randomized clinical trial suggest that patients with distal radius fractures that were managed with topology-optimized splints had better wrist functional outcomes and fewer complications at 6 weeks compared with those who received casting, with no difference at week 12. Therefore, topology-optimized splints with improved performance have the potential to be an advisable approach in the management of distal radius fractures. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000036480.