Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study.

BACKGROUND: The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR. METHODS: Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model. RESULTS: This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up. CONCLUSIONS: The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

Rapid recurrence and malignant transformation of a benign meningioma after pregnancy: a case report.

We report rapid recurrence and malignant transformation of a benign meningioma during pregnancy in a young woman. A 30-year-old female meeted an operation of benign meningioma (WHO Grade I) before her pregnancy. No signs of recurrence were found in MRI two months before her pregnancy. Subsequent MRI was performed 6 months after her giving birth. MRI results showed a recurrent meningioma with a size of 45 × 49 × 32 mm. Reoperation was performed later, histopathological workup showed an atypical meningothelial meningioma(WHO Grade II) with a Ki-67 level of about 10% and a PR expression above 70%; no ER was observed. To our best knowledge, this is the first report of the rapid malignant transformation of a benign meningioma during pregnancy.

Comprehensive analysis of the LncRNAs, MiRNAs, and MRNAs acting within the competing endogenous RNA network of LGG.

Messenger RNA (mRNA) and long noncoding RNA (lncRNA) targets interact via competitive microRNA (miRNA) binding. However, the roles of cancer-specific lncRNAs in the competing endogenous RNA (ceRNA) networks of low-grade glioma (LGG) remain unclear. This study obtained RNA sequencing data for normal solid tissue and LGG primary tumour tissue from The Cancer Genome Atlas database. We used a computational method to analyse the relationships among the mRNAs, lncRNAs, and miRNAs in these samples. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to predict the biological processes (BPs) and pathways associated with these genes. Kaplan-Meier survival analysis was used to evaluate the association between the expression levels of specific mRNAs, lncRNAs, and miRNAs and overall survival. Finally, we created a ceRNA network describing the relationships among these mRNAs, lncRNAs, and miRNAs using Cytoscape 3.5.1. A total of 2555 differentially expressed (DE) mRNAs, 218 DElncRNAs, and 192 DEmiRNAs were identified using R. In addition, GO and KEGG pathway analysis of the mRNAs and lncRNAs in the ceRNA network identified 10 BPs, 10 cell components, 10 molecular functions, and 48 KEGG pathways as selectively enriched. A total of 55 lncRNAs, 50 miRNAs, and 10 mRNAs from this network were shown to be closely associated with overall survival in LGG. Finally, 59 miRNAs, 235 mRNAs, and 17 lncRNAs were used to develop a ceRNA network comprising 313 nodes and 1046 edges. This study helps expand our understanding of ceRNA networks and serves to clarify the underlying pathogenesis mechanism of LGG.

Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 µg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in the annual decline in the FEV1 before and after bronchodilator use from day 30 to month 24. RESULTS: Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (±SE) annual decline in the FEV1 before bronchodilator use: the decline was 38±6 ml per year in the tiotropium group and 53±6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P=0.06). In contrast, the annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P=0.006). The incidence of adverse events was generally similar in the two groups. CONCLUSIONS: Tiotropium resulted in a higher FEV1 than placebo at 24 months and ameliorated the annual decline in the FEV1 after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).

The effects of incretin-based therapies on ß-cell function and insulin resistance in type 2 diabetes: A systematic review and network meta-analysis combining 360 trials.

AIM: To evaluate the comparative effects of incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4Is), on ß-cell function and insulin resistance in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Medline, Embase, the Cochrane Library and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) with a duration of at least 4 weeks. Network meta-analysis was performed, followed by subgroup analysis and meta-regression. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Outcomes of interest include homeostasis model assessment for ß cell function (HOMA-ß) and insulin resistance (HOMA-IR), fasting C-peptide and fasting plasma glucose (FPG). Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: A total of 360 RCTs (74% at least double-blinded) with 157 696 patients were included. Incretin-based therapies were compared with six other classes of glucose-lowering drugs or with placebo. Compared with placebo, a significant increase in HOMA-ß and fasting C-peptide was detected for GLP-1RAs (WMD = 20.31 [95% CI, 16.34-24.39] with low quality; WMD = 0.16 ng/mL [95% CI, 0.03-0.29] with low quality) and for DPP-4Is (WMD = 9.90 [95% CI, 8.27-11.61] with moderate quality; WMD = 0.09 ng/mL [95% CI, 0.04-0.14] with moderate quality) separately, while a significant reduction in HOMA-IR and FPG were found in favour of GLP-1RAs (WMD = -0.67 [95% CI, -1.08 to -0.27] with low quality; WMD = -1.04 mmol/L [95% CI, -1.26 to -0.83] with moderate quality) and DPP-4Is (WMD = -0.23 [95% CI, -0.38 to -0.08] with low quality; WMD = -0.77 mmol/L [95% CI, -0.98 to -0.57] with moderate quality), respectively. CONCLUSIONS: Incretin-based therapies not only show an increase in HOMA-ß and fasting C-peptide level, but also achieve a reduction in HOMA-IR and FPG in comparison with placebo. Although GRADE scores indicate low to moderate for most comparisons, incretin-based therapies seem to be an advisable option for long-term treatment to preserve ß-cell function.

Aptamer and its applications in neurodegenerative diseases.

Aptamers are small single-stranded DNA or RNA oligonucleotide fragments or small peptides, which can bind to targets by high affinity and specificity. Because aptamers are specific, non-immunogenic and non-toxic, they are ideal materials for clinical applications. Neurodegenerative disorders are ravaging the lives of patients. Even though the mechanism of these diseases is still elusive, they are mainly characterized by the accumulation of misfolded proteins in the central nervous system. So it is essential to develop potential measures to slow down or prevent the onset of these diseases. With the advancements of the technologies, aptamers have opened up new areas in this research field. Aptamers could bind with these related target proteins to interrupt their accumulation, subsequently blocking or preventing the process of neurodegenerative diseases. This review presents recent advances in the aptamer generation and its merits and limitations, with emphasis on its applications in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathy, Huntington's disease and multiple sclerosis.

CDC20 with malignant progression and poor prognosis of astrocytoma revealed by analysis on gene expression.

The malignant transformation of astrocytoma may result from the accumulation of multiple genetic alterations. Current research shows that diffuse astrocytoma (AIIs, WHO grade II) is inherently predisposed to recur locally, and to spontaneously progress to anaplastic astrocytoma (AAIIIs, WHO grade III) and eventually secondary glioblastoma (sGBMIVs, WHO grade IV). The aim of the study was to identify and validate the important gene(s) associated with malignant progression and poor prognosis of astrocytoma. Average expression levels of 82 samples (35 AIIs, 13 AAIIIs and 34 sGBMIVs) were compared to each other through no-paired student test. Candidate genes were screened by DAVID and Kaplan-Meier survival analysis. Further, the significant candidate genes were validated through real-time PCR(qPCR), western blot and immunohistochemistry (IHC) in different grades of glioma. Finally, the association of target gene and clinical molecular characterization was analyzed by Chi-squared analysis. The cell-division cycle protein 20(CDC20, p = 0.0129) and the polo-like kinase 1(PLK1, p = 0.0046) were screened by statistical and Kaplan-Meier survival analysis. The expression levels of CDC20 and PLK1 rose significantly through real-time PCR(qPCR), western blot and IHC. A chi-squared analysis showed that patients with CDC20 high-expression differ from patients with CDC20 low-expression in terms of WHO classification (p < 0.0001), karnofsky performance score (KPS, p < 0.0001), isocitrate dehydrogenase mutation (IDH1, p < 0.0001), phosphatase and tensin homolog mutation (PTEN, p = 0.027) and epidermal growth factor receptor protein amplification (EGFR, p = 0.048). Moreover, the biological processes analyses indicate CDC20 might have an essential role in astrocyte cell proliferation. We demonstrated that the expression level of CDC20 increases significantly along with malignant progression and poor prognosis of astrocytoma.

Long-term effects of laparoscopic sleeve gastrectomy versus roux-en-Y gastric bypass for the treatment of Chinese type 2 diabetes mellitus patients with body mass index 28-35 kg/m(2).

BACKGROUND: To compare long term effects of two bariatric procedures for Chinese type 2 diabetes mellitus (T2DM) patients with a body mass index (BMI) of 28-35 kg/m(2). METHODS: Sixty four T2DM patients with Glycated hemoglobin A1c (HbA1c) ≧ 7.0 % were randomly assigned to receive laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedure. Weight, percentage of excess weight loss (%EWL), BMI, waist circumference, HbA1c, fasting blood glucose (FBG), and C-peptide were measured. Serum lipid levels were also measured during three-year postoperative follow-up visits. RESULTS: Fifty five patients completed the 36-month follow-up. Both groups had similar baseline anthropometric and biochemical measures. At the end point, 22 patients (78.6 %) in SG group and 23 patients (85.2 %) in RYGB group achieved complete remission of diabetes mellitus with HbA1c < 6.0 % (P = 0.525) and without taking diabetic medications, and 25 patients in each group (89.3 % vs. 92.6 %) gained successful treatment of diabetes with HbA1c≦6.5 % (P = 0.100). Change in HbA1c, FBG and C peptide were comparable in the two groups. The RYGB group had significantly greater weight loss than the SG group [percentage of total weight loss (%TWL) of 31.0 % vs. 27.1 % (P = 0.049), %EWL of 92.3 % vs. 81.9 % (P = 0.003), and change in BMI of 11.0 vs. 9.1 kg/m(2)(P = 0.017), respectively]. Serum lipids in each group were also greatly improved. CONCLUSION: In this three-year study, SG had similar positive effects on diabetes and dyslipidemia compared to RYGB in Chinese T2DM patients with BMI of 28-35 kg/m(2). Longer term follow-ups and larger sample studies are needed to confirm these outcomes, however.

The Nonlinear Relationship Between High-Density Lipoprotein and Changes in Pulmonary Structure Function and Pulmonary Function in COPD Patients in China.

Background: The previous findings on the correlation between spirometry and high-density lipoprotein (HDL) cholesterol are intriguing yet conflicting. The aim of this research is to evaluate the relationship between HDL levels and spirometry as well as imaging parameters in patients with chronic obstructive pulmonary disease (COPD) in China. Methods: This study encompasses a total of 907 COPD patients. Participants with complete data from questionnaire interviews, lipid profile examinations, spirometry testing, and computed tomography (CT) scans were included in the analysis. A generalized additive model was employed to identify the non-linear relationship between HDL levels and both spirometry and imaging parameters. In the presence of non-linear correlations, segmented linear regression model was applied to ascertain threshold effects. Results: After adjusting for various factors, we found a non-linear correlation between HDL levels and spirometry/imaging parameters, with an inflection point at 4.2 (66 mg/dL). When Ln (HDL) was below 4.2, each unit increase correlated significantly with reduced post-bronchodilator FEV1 (0.32L, 95% CI: 0.09-0.55), decreased predicted FEV1% (11.0%, 95% CI: 2.7-19.3), and lowered FEV1/FVC (8.0%, 95% CI: 4.0-12.0), along with notable increases in Ln (LAA-950) by 1.20 (95% CI: 0.60-1.79) and Ln (LAA-856) by 0.77 (95% CI: 0.37-1.17). However, no significant associations were observed when Ln (HDL) was greater than or equal to 4.2. Conclusion: A non-linear correlation existed between HDL levels with lung function and CT imaging in COPD patients. Prior to reaching 66 mg/dL, an elevation in HDL was significantly associated with impaired lung function, more severe gas trapping and emphysema.

Clinical Characteristics and 2-Year Outcomes of Chronic Obstructive Pulmonary Disease Patients With High Blood Eosinophil Counts: A Population-based Prospective Cohort Study in China.

BACKGROUND: High blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community. METHODS: We obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/µL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma. RESULTS: Of the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09-1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results. CONCLUSIONS: COPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China.

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

A high efficiency dual-junction solar cell implemented as a nanowire array.

In this work, we present an innovative design of a dual-junction nanowire array solar cell. Using a dual-diameter nanowire structure, the solar spectrum is separated and absorbed in the core wire and the shell wire with respect to the wavelength. This solar cell provides high optical absorptivity over the entire spectrum due to an electromagnetic concentration effect. Microscopic simulations were performed in a three-dimensional setup, and the optical properties of the structure were evaluated by solving Maxwell's equations. The Shockley-Queisser method was employed to calculate the current-voltage relationship of the dual-junction structure. Proper design of the geometrical and material parameters leads to an efficiency of 39.1%.

Cognitive protection of incretin-based therapies in patients with type 2 diabetes mellitus: A systematic review and meta-analysis based on clinical studies.

AIMS/INTRODUCTION: Cognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognized as an important complication of type 2 diabetes mellitus. The aims of the preset study was to investigate the cognitive protection of incretin-based therapies, including glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: PubMed, EMBASE, Cochrane library, Web of Science and PsycINFO were searched from the inception through 17 January 2023 for randomized controlled trials and cohort studies on the association between incretin-based therapies and cognitive function. A total of 15 studies were finally included in our systematic review, and eight of which were incorporated into our meta-analysis. RESULTS: Pooled results showed that the Mini-Mental State Examination score in incretin-based therapy groups was increased by 1.20 compared with the control group (weighted mean difference 1.20, 95% confidence interval 0.39-2.01). The results of eight studies assessed by the Newcastle Ottawa Quality Assessment Scale and the Cochrane Collaboration's tool, and the quality of the eight studies were at a relatively high level. Egger's regression did not show significant publication bias. CONCLUSIONS: Current evidence shows that incretin-based therapies might be more effective, when compared with the other hypoglycemic drugs, for cognitive improvement in patients with type 2 diabetes mellitus.

Comparative effectiveness of different hepatocellular carcinoma screening intervals or modalities: a systematic review and meta-analysis.

BACKGROUND: Current guidelines recommend hepatocellular carcinoma (HCC) screening in high-risk populations. However, the ideal HCC screening interval and screening modality have not been determined. This study aimed to compare the screening efficacy among different modalities with various intervals. METHODS: PubMed and other nine databases were searched through June 30, 2021. Binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs). Survival rates were also pooled using RR with 95% CIs because most eligible studies only provided the number of survival patients instead of hazard ratio. RESULTS: In all, 13 studies were included. Two random controlled trials (RCTs) and six cohort studies compared screening intervals for ultrasonography (US) screening and found no significant differences between shorter (3- or 4-month) and longer (6- or 12-month) screening intervals in terms of early HCC proportion, HCC significant mortality, 1-year survival rate; screening at 6-month interval significantly increased the proportion of early HCC (RR = 1.17, 95% confidence interval [CI]: 1.08-1.26) and prolonged the 5-year survival rate (RR = 1.39, 95% CI: 1.07-1.82) relative to the 12-month interval results. Three other RCTs and two cohort studies compared different screening modalities in cirrhosis or chronic hepatitis B, which indicated no statistical differences in the proportion of early HCC (RR = 0.89, 95% CI: 0.40-1.96) and HCC mortality (RR = 0.69, 95% CI: 0.23-2.09) between the biannual US and annual computed tomography (CT screening). Biannual US screening showed a lower proportion of early HCC than biannual magnetic resonance imaging (MRI) (RR = 0.60, 95% CI: 0.37-0.97) and biannual US combined with annual CT (RR = 1.31, 95% CI: 1.13-1.51) screening. The proportion of early HCC in the contrast-enhanced US group was slightly higher than that in the B-mode US (RR = 1.08, 95% CI: 1.00-1.23) group. CONCLUSIONS: The evidence suggests that 6 months may be the best HCC screening interval for US screening. The effectiveness of CT and MRI is better than US during same screening intervals. However, MRI and CT are more expensive than US, and CT also can increase the risk of radiation exposure. The selection of CT or MRI instead of US should be carefully considered. REGISTRATION: No. CRD42020148258 at PROSPERO website ( https://www.crd.york.ac.uk/PROSPERO/ ).

Benefits and harms of screening for hepatocellular carcinoma in high-risk populations: systematic review and meta-analysis.

Objective: The incidence and mortality of hepatocellular carcinoma (HCC) have been increasing around the world. Current guidelines recommend HCC screening in high-risk population. However, the strength of evidence of benefits and harms of HCC screening to support the recommendation was unclear. The objective is to systematically synthesize current evidence on the benefits and harms of HCC screening. Methods: We searched PubMed and nine other databases until August 20, 2021. We included cohort studies and RCTs that compared the benefits and harms of screening and non-screening in high-risk population of HCC. Case series studies that reported harms of HCC screening were also included. Pooled risk ratio (RR), according to HCC screening status, was calculated for each benefit outcome (e.g., HCC mortality, survival rate, proportion of early HCC), using head-to-head meta-analysis. The harmful outcomes (e.g., proportion of physiological harms provided by non-comparative studies were pooled by prevalence of meta-analysis. Analysis on publication bias and quality of life, subgroup analysis, and sensitivity analysis were also conducted. Results: We included 70 studies, including four random clinical trials (RCTs), 63 cohort studies,three case series studies. The meta-analysis of RCTs showed HCC screening was significantly associated with reduced HCC mortality (RR [risk ratio], 0.73 [95% CI, 0.56-0.96]; I 2 = 75.1%), prolonged overall survival rates (1-year, RR, 1.72 [95% CI, 1.13-2.61]; I 2 = 72.5%; 3-year, RR, 2.86 [95% CI, 1.78-4.58]; I 2 = 10.1%; and 5-year, RR, 2.76 [95% CI, 1.37-5.54]; I 2 = 28.3%), increased proportion of early HCC detection (RR, 2.68 [95% CI, 1.77-4.06]; I 2 = 50.4%). Similarly, meta-analysis of cohort studies indicated HCC screening was more effective than non-screening. However, pooled proportion of physiological harms was 16.30% (95% CI: 8.92%-23.67%) and most harms were of a mild to moderate severity. Conclusion: The existing evidence suggests HCC screening is more effective than non-screening in high-risk population. However, harms of screening should not be ignored.

Inter-relationships among neutrophilic inflammation, air trapping and future exacerbation in COPD: an analysis of ECOPD study.

BACKGROUND: The inter-relationships among neutrophilic airway inflammation, air trapping and future exacerbation in chronic obstructive pulmonary disease (COPD) remain unclear. OBJECTIVE: To evaluate the associations between sputum neutrophil proportions and future exacerbation in COPD and to determine whether these associations are modified by significant air trapping. METHODS: Participants with completed data were included and followed up to the first year in the Early Chronic Obstructive Pulmonary Disease study (n=582). Sputum neutrophil proportions and high-resolution CT-related markers were measured at baseline. Sputum neutrophil proportions were dichotomised based on their median (86.2%) to low and high levels. In addition, subjects were divided into the air trapping or non-air trapping group. Outcomes of interest included COPD exacerbation (separately any, severe and frequent exacerbation, occurring in the first year of follow-up). Multivariable logistic regressions were performed to examine the risk of severe exacerbation and frequent exacerbation with either neutrophilic airway inflammation groups or air trapping groups. RESULTS: There was no significant difference between high and low levels of sputum neutrophil proportions in the exacerbation in the preceding year. After the first year of follow-up, subjects with high sputum neutrophil proportions had increased risks of severe exacerbation (OR=1.68, 95% CI: 1.09 to 2.62, p=0.020). Subjects with high sputum neutrophil proportions and significant air trapping had increased odds of having frequent exacerbation (OR=3.29, 95% CI: 1.30 to 9.37, p=0.017) and having severe exacerbation (OR=2.72, 95% CI: 1.42 to 5.43, p=0.003) when compared with those who had low sputum neutrophil proportions and non-air trapping. CONCLUSIONS: We found that subjects with high sputum neutrophil proportions and significant air trapping are prone to future exacerbation of COPD. It may be a helpful predictor of future exacerbation.

Clinical features and 1-year outcomes of chronic bronchitis in participants with normal spirometry: results from the ECOPD study in China.

BACKGROUND: Evidence regarding clinical features and outcomes of individuals with non-obstructive chronic bronchitis (NOCB) remains scarce, especially in never-smokers. We aimed to investigate the clinical features and 1-year outcomes of individuals with NOCB in the Chinese population. METHODS: We obtained data on participants in the Early Chronic Obstructive Pulmonary Disease Study who had normal spirometry (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ≥0.70). NOCB was defined as chronic cough and sputum production for at least 3 months for two consecutive years or more at baseline in participants with normal spirometry. We assessed the differences in demographics, risk factors, lung function, impulse oscillometry, CT imaging and frequency of acute respiratory events between participants with and without NOCB. RESULTS: NOCB was present in 13.1% (149/1140) of participants with normal spirometry at baseline. Compared with participants without NOCB, those with NOCB had a higher proportion of men and participants with smoke exposure, occupational exposure, family history of respiratory diseases and worse respiratory symptoms (all p<0.05), but there was no significant difference in lung function. Never-smokers with NOCB had higher rates of emphysema than those without NOCB, but airway resistance was similar. Ever-smokers with NOCB had greater airway resistance than those without NOCB, but emphysema rates were similar. During 1-year follow-up, participants with NOCB had a significantly increased risk of acute respiratory events compared with participants who did not have NOCB, after adjustment for confounders (risk ratio 2.10, 95% CI 1.32 to 3.33; p=0.002). These results were robust in never-smokers and ever-smokers. CONCLUSIONS: Never-smokers and ever-smokers with NOCB had more chronic obstructive pulmonary disease-related risk factors, evidence of airway disease and greater risk of acute respiratory events than those without NOCB. Our findings support expanding the criteria defining pre-COPD to include NOCB.

Machine learning analysis of humoral and cellular responses to SARS-CoV-2 infection in young adults.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces B and T cell responses, contributing to virus neutralization. In a cohort of 2,911 young adults, we identified 65 individuals who had an asymptomatic or mildly symptomatic SARS-CoV-2 infection and characterized their humoral and T cell responses to the Spike (S), Nucleocapsid (N) and Membrane (M) proteins. We found that previous infection induced CD4 T cells that vigorously responded to pools of peptides derived from the S and N proteins. By using statistical and machine learning models, we observed that the T cell response highly correlated with a compound titer of antibodies against the Receptor Binding Domain (RBD), S and N. However, while serum antibodies decayed over time, the cellular phenotype of these individuals remained stable over four months. Our computational analysis demonstrates that in young adults, asymptomatic and paucisymptomatic SARS-CoV-2 infections can induce robust and long-lasting CD4 T cell responses that exhibit slower decays than antibody titers. These observations imply that next-generation COVID-19 vaccines should be designed to induce stronger cellular responses to sustain the generation of potent neutralizing antibodies.

[Application of intraoperative contrast-enhanced ultrasound in different pathological grades of glioma].

OBJECTIVE: To explore the feasibility and value of intra-operative contrast-enhanced ultrasound in different pathological grades of glioma. METHODS: A total of 46 patients with glioma were selected to undergo the contrast-enhanced ultrasound. They were divided into 3 groups according to their pathological grades. RESULTS: All 46 tumors were hyperechoic after examinations and the borders became much more distinct. Different level of tumors had their representative ultrasonic findings. CONCLUSIONS: Intraoperative contrast-enhanced ultrasound is quite useful for determining the position and border of tumors. And it is also excellent in detecting the residual tumor tissues post-operatively. And it can improve the resection accuracy and operative precision, especially for Grade IV glioma with internal necrosis, cyst and surrounding brain edema.

Polo-like kinases as potential targets and PLK2 as a novel biomarker for the prognosis of human glioblastoma.

The most prevalent malignant central nervous system (CNS) cancer is glioblastoma multiforme (GBM). PLKs (polo-like kinases) are a kind of serine-threonine kinase that modulate DNA replication, mitosis, and stress responses. PLKs in GBM need to be better studied and examined in terms of their expression, function, along with prognostic significance. Using an existing publicly available data set, we evaluated the expression level and prognostic relevance of PLKs in GBM patients at the molecular level. The biological processes along with cascades of the screened gene were predicted using the functional enrichment of Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways. The data illustrated that PLK1/3/4 contents were greater in GBM tissues than in non-tumorous tissues, but PLK2/5 expression levels were lower. PLK2 expression was also linked to patient outcome in GBM. Our findings imply that PLKs might be useful molecular indicators as well as prospective treatment targets for GBM. A PLK2 inhibitor has been studied for the first time in a glioma cell in this work. In glioma cells, ON1231320 has anticancer effects. Finally, a summary of PLK inhibitors is presented, along with projections for future progress.