Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.

Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

ObjectiveTo explore the association between short-term exposure to atmospheric fine particulate matter （PM_2.5） and ozone （O₃） and systemic inflammatory indicators in patients with pneumonia， and to identify the susceptible populations. MethodsFrom September 2018 to April 2020， data of 1 480 patients admitted for pneumonia was collected from a tertiary hospital in Taiyuan City. Generalized additive models （GAMs） were used to explore the associations between PM_2.5 and O₃ exposure and inflammatory indicators of patients with pneumonia； and to explore the susceptibility factors and susceptible populations to PM_2.5 and O₃ exposures through stratified analyses. ResultsThe short-term exposure to PM_2.5 was associated with changes in peripheral blood C-reation protein （CRP）， erythrocyte sedimentation （ESR）， easinophil （EOS）， neutrophil （NEU） and neutrophil-lymphocyte ratio （NLR） in patients with pneumonia， and there were different degrees of hysteresis effects， with the effect values reaching a maximum at lag03， lag03， lag0， lag03， lag03， respectively， which were 4.13% （95%CI： 0.43%‒7.84%）， 3.10% （95%CI： 0.24%‒5.97%）， 5.27% （95%CI： 3.12%‒7.42%）， 1.85% （95%CI： 0.36%‒3.34%）， and 2.53% （95%CI： 0.53%‒4.74%） for every 10 μg·m^-3 of PM_2.5. The changes in O₃ concentration were associated with the elevation of peripheral blood PCT and ESR in patients with pneumonia， and their effect values all reached the maximum at lag01 d， every 1 μg·m^-3 of O₃ elevation increased by 0.38% （95%CI： 0.04%‒0.73%） and 0.47% （95%CI： 0.19%‒0.76%）， respectively. Stratified analyses showed that the associations of PM_2.5 with peripheral blood CRP， ESR， NEU， and NLR in pneumonia patients were more significant in males， the elderly， and those with onset in the cold season； the associations of O₃ with peripheral blood PCT and ESR in pneumonia patients were more significant in the elderly and those with onset in the warm season， and the peripheral blood CRP and PCT in female patients with pneumonia were more susceptible to the changes of O₃. ConclusionShort-term exposure to atmospheric PM_2.5 and O₃ are positively associated with changes in inflammatory indicators in patients with pneumonia， and the effects of PM_2.5 on patients with pneumonia are more extensive than those of O₃， with a longer lag effect. In addition， elderly patients with pneumonia are more sensitive to air pollution， male patients with pneumonia are more sensitive to PM_2.5， and female patients with pneumonia are more sensitive to O₃. Cold and warm seasons can exacerbate the effects of PM_2.5 and O₃ on inflammatory indicators in patients with pneumonia， respectively， and the patients must be protected well.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.