Clinical significance of FEV0.5 and FEV0.75 in the determination of pulmonary function in children with bronchial asthma

Objective·To evaluate the abnormal rates of measured/predicted values of forced expiratory volume in 0.5 second (FEV0.5) and FEV0.75 in lung ventilation function testing, as well as the clinical significance of different cut-off points for improvement rates before and after bronchodilation testing in the diagnosis of children with bronchial asthma (asthma).Methods·From January 2020 to February 2021, school-age children diagnosed with asthma during their hospitalization at the Children's Hospital, Zhejiang University School of Medicine were selected. The data on lung ventilation function testing and bronchodilator testing were collected. The difference in abnormal rates of measured/predicted values of FEVt in children in lung ventilation function testing was compared. Diagnostic test four grid table was used to analyze the sensitivity and specificity of different cut-off points for the improvement rates of FEV0.5 and FEV0.75 in the diagnosis of asthma before and after bronchodilation testing.Results·A total of 148 children were included. All enrolled cases completed lung ventilation function testing, with 51 cases completing bronchodilation testing simultaneously. The results of lung ventilation function testing showed that 21 patients had obstructive ventilation dysfunction, 30 patients had small airway dysfunction, and the remaining patients had normal, restrictive or mixed ventilation dysfunction. The results of bronchodilation testing showed that in the 51 asthmatic children with obstructive ventilation dysfunction and small airway dysfunction, 22 of them were positive for bronchodilation testing. The comparison of the abnormal rates of FEVt measured/predicted values showed that the abnormal rates of FEV0.75 measured/predicted values were higher than those of FEV1 and FEV0.5 (χ2=10.18, P=0.000; χ2=10.95, P=0.000). The sensitivity and specificity analysis results of different cut-off points for the improvement rates of EFV0.75 and FEV0.5 showed that the cut-off point for FEV0.5 improvement rate at 16% had very high sensitivity and specificity, with the highest Jordan index; the cut-off points for FEV0.75 improvement rate were 12% and 14%, respectively, with sensitivity and specificity reaching 100%.Conclusion·The measured/predicted value of FEV0.75 in lung ventilation function testing can be considered as an alternative indicator for the measured/predicted value of FEV1 to further evaluate the presence of obstructive ventilation dysfunction. On the basis of the results of bronchodilation testing, it can be considered to analyze the airway reversibility by combining the best cut-off points of FEV0.75 and FEV0.5 improvement rates, in order to enhance the clinical value of bronchodilation testing in the diagnosis of asthma

Congrong Shujing Granule-Induced GRP78 Expression Reduced Endoplasmic Reticulum Stress and Neuronal Apoptosis in the Midbrain in a Parkinson’s Disease Rat Model

The main pathological changes inherent in Parkinson’s disease (PD) are degeneration and loss of dopamine neurons in the midbrain and formation of Lewy bodies. Many studies have shown that the pathogenesis of PD is closely related to endoplasmic reticulum (ER) oxidative stress. This study combined various traditional Chinese medicines to prepare Congrong Shujing granules (CSGs). The optimal dose combination of the ingredients was identified by experimental intervention in SH-SY5Y cells in vitro. A PD rat model was established by intraperitoneal injection of rotenone sunflower oil emulsion. The suspension tests were performed on the 14th day after modeling and also on the 14th day after CSG intervention (5.88 g/kg, 11.76 g/kg, and 23.52 g/kg). We evaluated the changes in motor function and the expression of neuronal cell functional marker proteins, ER stress (ERS) marker proteins, and apoptosis-related pathway proteins of neuronal cells. Changes in cellular ultrastructure were observed by electron microscopy. Our results showed that CSG treatment lengthened the duration of PD rats’ gripping to the wire. 78 kDa glucose-regulated protein (GRP78) expression in the substantia nigra was significantly upregulated in the middle- and high-dose CSG groups after 14 days of treatment compared with the model group. The expression of the key dopaminergic neuron functional enzyme tyrosine hydroxylase (TH) and cerebral dopamine neurotrophic factor (CDNF) was elevated. The expression of c-Jun N-terminal kinase (JNK) and phosphorylated c-Jun decreased, and cell apoptosis was significantly reduced. Compared with the model group, the treatment groups had fewer ER fragmentation and degranulation (ribosome shedding) and abundant ER and mitochondria suggesting that CSG reduced ER stress and neuronal apoptosis in the midbrain of a PD rat model by inducing the expression of molecular chaperone GRP78

Pulmonary delivery of mucus-traversing PF127-modified silk fibroin nanoparticles loading with quercetin for lung cancer therapy

The mucosal barrier remains a major barrier in the pulmonary drug delivery system, as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles (NPs). Herein, we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin (marked as QR-SF (PF127) NPs), aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR. The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins, thus facilitating the diffusion of SF(PF127) NPs in the mucus layer. The QR-SF (PF127) NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties. Fluorescence recovery after photobleaching (FRAP) assay and transepithelial transport test showed that QR-SF (PF127) NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model. Notably, a large amount of QR-SF (PF127) NPs distributed uniformly in the mice airway section, indicating the good retention of NPs in the respiratory tract. The mice melanoma lung metastasis model was established, and the therapeutic effect of QR-SF (PF127) NPs was significantly improved in vivo. PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhance mucus penetration efficiency in the pulmonary drug delivery system

Selective COX-2 inhibitors do not increase gastrointestinal reactions after colorectal cancer surgery: a systematic review and meta-analysis

Abstract Background The effectiveness of selective COX-2 inhibitors in preventing colorectal cancer recurrence has been demonstrated, however it is unknown how safe and successful they will be over the long term. As a result, we looked at the efficacy, safety, and consequences of adding COX-2 inhibitors to the treatment plan afterward. Methods In patients with advanced colorectal cancer, we compared the efficacy of celecoxib at two different doses (200 mg twice day and 400 mg twice daily) with placebo. To evaluate the impacts of post-treatment, several datasets from inception to June 2022 were searched. Response rate, illness control rate, and 3-year survival were the main results. And evaluated several safety outcomes, particularly those that were susceptible to adverse events. Results The study comprised a total of 9 randomized controlled trials (3206 participants). Celecoxib and rofecoxib doidn’t significantly improved the 1–3 year remission rate (OR, 1.57 [95% CI: 0.95–2.57]) and disease control rate (OR, 1.08 [95% CI: 0.99–1.17]). Subgroup analysis of different doses showed that 400 mg of celecoxib significantly improved the response rate (OR, 2.82 [95%CI: 1.20–6.61]). 200 mg celecoxib was not significant (OR, 1.28 [95% CI: 0.66–2.49]). Rofecoxib also did not fully improve disease response rates. Celecoxib at any dose improved 3-year survival (OR, 1.21 [95% CI: 1.02–1.45]). It is important to note that COX-2 inhibitors did not significantly enhance the likelihood of adverse events including gastrointestinal or cardiovascular side effects at any dose. Conclusions For patients with advanced colorectal cancer, a reasonable chemoprevention regimen can include celecoxib 400 mg twice daily

Salivary IgG4 Levels Contribute to Assessing the Efficacy of <i>Dermatophagoides pteronyssinus</i> Subcutaneous Immunotherapy in Children with Asthma or Allergic Rhinitis

At present, there are no effective, non-invasive, and objective indicators to evaluate the efficacy of pediatric house dust mite (HDM)-specific allergen immunotherapy (AIT). A prospective, observational study was performed in children with Dermatophagoides pteronyssinus (Der p) asthma and/or allergic rhinitis (AR). Forty-four patients received subcutaneous Der p-AIT for 2 years, and eleven patients received only symptomatic treatment. The patients needed to finish their questionnaires at each visit. Serum and salivary Der p-specific IgE, IgG4, and IgE-blocking factors (IgE-BFs) were measured at 0, 4, 12, and 24 months during AIT. A correlation between them was also evaluated. Subcutaneous Der p-specific AIT improved the clinical symptoms of children with asthma and/or AR. The Der p-specific IgE-BF significantly increased at 4, 12, and 24 months after AIT treatment. Serum and salivary Der p-specific IgG4 significantly increased with the time of the AIT treatment, and significant correlations between them at different time points were observed (p Der p-specific IgE-BF and Der p-specific IgG4 at the baseline, 4, 12, and 24 months after the AIT (p Der p-specific IgG4 levels also demonstrated a certain correlation with the Der p-specific IgE-BF. Der p-specific AIT is an effective treatment for children with asthma and/or AR. Its effect was associated with increased serum and salivary-specific IgG4 levels, as well as an increased IgE-BF. Non-invasive salivary-specific IgG4 may be useful for monitoring the efficacy of AIT in children

Mechanisms of Cong Rong Shu Jing Compound Effects on Endoplasmic Reticulum Stress in a Rat Model of Parkinson’s Disease

This study investigated the effects of the Cong Rong Shu Jing (CRSJ) compound on endoplasmic reticulum stress in a rat model of Parkinson's disease (PD). A total of 40 rats were subcutaneously injected with rotenone-sunflower oil emulsion into the back of the neck to establish a rat model of PD. These PD rats were randomly divided into low-, medium-, and high-dose groups (intragastric administration of 0.5, 1, and 2 g/kg CRSJ, respectively) and a model group (intragastric administration of the solvent; 10 rats per group). Furthermore, 10 rats each were attributed to the control and vehicle groups (both received intragastric administration of the CRSJ solvent, and the vehicle group were injected additionally with sunflower oil alone). A traction test was conducted two times, after the PD model establishment and after 14 days of CRSJ gavage. The numbers of tyrosine hydroxylase- (TH-) positive cells and the dopamine levels in the substantia nigra were assessed using immunohistochemistry and high-performance liquid chromatography, respectively. Western blotting detected the expression levels of α-synuclein, endoplasmic reticulum stress pathways-related proteins, cerebral dopamine neurotrophic factor (CDNF), mesencephalic astrocyte-derived neurotrophic factor (MANF), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related proteins. Compared with the model group, the number of TH-positive cells in the substantia nigra was increased in the CRSJ groups. The expression levels of α-synuclein and the endoplasmic reticulum stress pathways-associated proteins glucose regulatory protein 78, inositol-requiring enzyme 1, apoptosis signal-regulating kinase 1, phosphorylated c-Jun N-terminal kinase, and caspase-12 were reduced. However, CRSJ administration elevated the expression levels of the neurotrophic factors CDNF and MANF, as well as those of p-PI3K and p-AKT. The CRSJ compound can relieve endoplasmic reticulum stress in PD rats and exerts protective effects in this animal model. These effects may be related to increased expression of neurotrophic factors and activation of the PI3K/AKT pathway

Distinct brain state dynamics of native and second language processing during narrative listening in late bilinguals

The process of complex cognition, which includes language processing, is dynamic in nature and involves various network modes or cognitive modes. This dynamic process can be manifested by a set of brain states and transitions between them. Previous neuroimaging studies have shed light on how bilingual brains support native language (L1) and second language (L2) through a shared network. However, the mechanism through which this shared brain network enables L1 and L2 processing remains unknown. This study examined this issue by testing the hypothesis that L1 and L2 processing is associated with distinct brain state dynamics in terms of brain state integration and transition flexibility. A group of late Chinese-English bilinguals was scanned using functional magnetic resonance imaging (fMRI) while listening to eight short narratives in Chinese (L1) and English (L2). Brain state dynamics were modeled using the leading eigenvector dynamic analysis framework. The results show that L1 processing involves more integrated states and frequent transitions between integrated and segregated states, while L2 processing involves more segregated states and fewer transitions. Our work provides insight into the dynamic process of narrative listening comprehension in late bilinguals and sheds new light on the neural representation of language processing and related disorders

Peroxidase-Like Activity of Ethylene Diamine Tetraacetic Acid and Its Application for Ultrasensitive Detection of Tumor Biomarkers and Circular Tumor Cells

Ethylene diamine tetraacetic acid (EDTA) is such a powerful chelating agent that it may form stable complexes with most metal ions, which has wide applications in industry, agriculture, environment, and pharmaceutical technology. Recently, EDTA was found to enhance the photocatalytic property of some materials. Inspired by this fact of EDTA in the photocatalytic role, we further investigated the photocatalytic property of EDTA and found much the same as that of natural horseradish peroxidase (HRP). This significant discovery of peroxidase-like property may extend the applications of conventional EDTA in life science. A novel and colorimetric sensor based on the peroxidase-like EDTA and unique gold nanorods (GNRs) was designed. Under light irradiation, EDTA may catalyze decomposition of hydrogen peroxide and in situ regulate the longitudinal plasmon wavelength (LPW) of GNRs, displaying various color solution as a read-out means. This colorimetric nanosensor has a great potential to develop into a platform to quantitatively determine analytes as long as the specific antibodies against them were available. Biomarkers of different diseases, such as breast cancer and prostate cancer, were detected with high accuracy. Moreover, combined with immunomagnetic separation of circulating tumor cells (CTCs) from blood, a visual read-out for detection of CTCs was established, which has promising applications in clinical diagnosis, environmental monitoring, and food quality control only using naked eyes