Unveiling the functional heterogeneity of cytokine-primed human umbilical cord mesenchymal stem cells through single-cell RNA sequencing.

BACKGROUND: Mesenchymal stem cells (MSCs) hold immense promise for use in immunomodulation and regenerative medicine. However, their inherent heterogeneity makes it difficult to achieve optimal therapeutic outcomes for a specific clinical disease. Primed MSCs containing a certain cytokine can enhance their particular functions, thereby increasing their therapeutic potential for related diseases. Therefore, understanding the characteristic changes and underlying mechanisms of MSCs primed by various cytokines is highly important. RESULTS: In this study, we aimed to reveal the cellular heterogeneity, functional subpopulations, and molecular mechanisms of MSCs primed with IFN-γ, TNF-α, IL-4, IL-6, IL-15, and IL-17 using single-cell RNA sequencing (scRNA-seq). Our results demonstrated that cytokine priming minimized the heterogeneity of the MSC transcriptome, while the expression of MSC surface markers exhibited only slight changes. Notably, compared to IL-6, IL-15, and IL-17; IFN-γ, TNF-α, and IL-4 priming, which stimulated a significantly greater number of differentially expressed genes (DEGs). Functional analysis, which included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, indicated that IFN-γ, TNF-α, and IL-4-primed hUC-MSCs are involved in interferon-mediated immune-related processes, leukocyte migration, chemotaxis potential, and extracellular matrix and cell adhesion, respectively. Moreover, an investigation of various biological function scores demonstrated that IFN-γ-primed hUC-MSCs exhibit strong immunomodulatory ability, TNF-α-primed hUC-MSCs exhibit high chemotaxis potential, and IL-4-primed hUC-MSCs express elevated amounts of collagen. Finally, we observed that cytokine priming alters the distribution of functional subpopulations of MSCs, and these subpopulations exhibit various potential biological functions. Taken together, our study revealed the distinct regulatory effects of cytokine priming on MSC heterogeneity, biological function, and functional subpopulations at the single-cell level. CONCLUSIONS: These findings contribute to a comprehensive understanding of the inflammatory priming of MSCs, paving the way for their precise treatment in clinical applications.

Application of computer-aided diagnosis to predict malignancy in BI-RADS 3 breast lesions.

Purpose: To evaluate the ability of computer-aided diagnosis (CAD) system (S-Detect) to identify malignancy in ultrasound (US) -detected BI-RADS 3 breast lesions. Materials and methods: 148 patients with 148 breast lesions categorized as BI-RADS 3 were included in the study between January 2021 and September 2022. The malignancy rate, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were calculated. Results: In this study, 143 breast lesions were found to be benign, and 5 breast lesions were malignant (malignancy rate, 3.4 %, 95 % confidence interval (CI): 0.5-6.3). The malignancy rate rose significantly to 18.2 % (4/22, 95 % CI: 2.1-34.3) in the high-risk group with a "possibly malignant" CAD result (p = 0.017). With a "possibly benign" CAD result, the malignancy rate decreased to 0.8 % (1/126, 95 % CI: 0-2.2) in the low-risk group (p = 0.297). The AUC, sensitivity, specificity, accuracy, PPV, and NPV of the CAD system in BI-RADS 3 breast lesions were 0.837 (95 % CI: 77.7-89.6), 80.0 % (95 % CI: 73.6-86.4), 87.4 % (95 % CI: 82.0-92.7), 87.2 % (95 % CI: 81.8-92.6), 18.2 % (95 % CI: 2.1-34.3) and 99.2 % (95 % CI: 97.8-100.0), respectively. Conclusions: CAD system (S-Detect) enables radiologists to distinguish a high-risk group and a low-risk group among US-detected BI-RADS 3 breast lesions, so that patients in the low-risk group can receive follow-up without anxiety, while those in the high-risk group with a significantly increased malignancy rate should actively receive biopsy to avoid delayed diagnosis of breast cancer.

Novel insights into the NOx emissions characteristics in PEMS tests of a heavy-duty vehicle under different payloads.

Real Drive Emission (RDE) test with Portable Emission Measurement System (PEMS) is a widely adopted way to assess vehicle emission compliance. However, the current NOx emissions calculation method stipulated in the China VI emission standard easily ignores the NOx emissions during cold start and low-power operation. To study the effect of cold start and low-power operation on the calculation of NOx emissions in the PEMS test, in this study, a China VI Heavy-Duty Vehicle (HDV) for urban use was used to conduct PEMS tests under various vehicle payload conditions. The data analysis results show that the increase in vehicle payload is beneficial to reducing the specific NOx emissions and passing the NOx emission compliance test because the increased payload improves the NOx conversion efficiency of the SCR system. Cold start duration has no obvious relationship with vehicle payload, accounting for only about 4∼6% in each test, but contributing more than 30% of NOx emissions. Due to the effect of the power threshold and the 90th cumulative percentile, the cold start data has little influence on the result of the NOx emissions assessment and the maximum variation of the NOx emissions result in this study is an 8% rise. For the HDV for urban use, the variation of the power threshold resulting from vehicle payload is small, no more than 2% in this study. The presence of the power threshold makes almost only the low-power operation in the second half of urban driving have an impact on the NOx emissions calculation, which may make more than 50% of NOx emissions in the PEMS test be neglected. The impact of the low-power operation on NOx emissions calculation result will be significantly enhanced if all windows are considered in the Moving Average Window (MAW) method. In the meantime, the degree of variation is closely related to the NOx emissions level during the first half of urban driving. The maximum deterioration of NOx emission assessment result can be more than 90% in this study.

Clinical Application of Computer-Aided Diagnosis System in Breast Ultrasound: A Prospective Multicenter Study.

OBJECTIVES: Ultrasound tends to present very high sensitivity but relatively low specificity and positive predictive value (PPV), which would result in unnecessary breast biopsies. The purpose of this study is to analyze the diagnostic performance of computer-aided diagnosis (CAD) (S-Detect) system in differentiating breast lesions and reducing unnecessary biopsies in non-university hospitals in less-developed regions of China. METHODS: The study was a prospective multicenter study from 8 hospitals. The ultrasound images, and cine, CAD analysis, and BI-RADS were recorded. The accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the curve (AUC) were analyzed and compared between CAD and radiologists. The Youden Index (YI) was used to determine optimal cut-off for the number of planes to downgrade. RESULTS: A total of 491 breast lesions were included in the study. Less-experienced radiologists combined CAD was superior to less-experienced radiologists alone in AUC (0.878 vs 0.712, p < 0.001), and specificity (81.3% vs 44.6%, p < 0.001). There was no statistical difference in AUC (0.891 vs 0.878, p = 0.346), and specificity (82.3% vs 81.3%, p = 0.791) between experienced radiologists and less-experienced radiologists combined CAD. With CAD assistance, the biopsy rate of less-experienced radiologists was significantly decreased (100.0% vs 25.6%, p < 0.001), and malignant rate of biopsy was significantly increased (15.0% vs 43.9%, p < 0.001). CONCLUSIONS: CAD system can be an effective auxiliary tool in differentiating breast lesions and reducing unnecessary biopsies for radiologists from non-university hospitals in less-developed regions of China.

Association between new plasma inflammatory markers and risk of colorectal neoplasms in individuals over 50 years old.

OBJECTIVE(S): The prognostic value of systemic cytokine profiles and inflammatory markers in colorectal cancer were explored by several studies. We want to know more about inflammatory biomarkers in colorectal adenoma and early cancer. METHOD: The level of 38 inflammatory markers in the plasma of 112 adenoma patients, 72 Tis-T1 staging of colorectal carcinoma patients, 34 T2-T4 staging of colorectal carcinoma patients and 53 normal subjects were detected and compared. RESULT(S): Eight inflammatory biomarkers (Eotaxin, GCSF, IL-4, IL-5, IL-17E, MCP-1, TNF-α and VEGF-A) have higher plasma concentrations in colorectal adenoma and cancer patients compared with normal participants over 50 years old. CONCLUSION(S): Inflammatory markers may have the prognostic value for colorectal adenoma and early-stage carcinoma.

Deep Learning-Based Computer-Aided Diagnosis for Breast Lesion Classification on Ultrasound: A Prospective Multicenter Study of Radiologists Without Breast Ultrasound Expertise.

BACKGROUND. Computer-aided diagnosis (CAD) systems for breast ultrasound interpretation have been primarily evaluated at tertiary and/or urban medical centers by radiologists with breast ultrasound expertise. OBJECTIVE. The purpose of this study was to evaluate the usefulness of deep learning-based CAD software on the diagnostic performance of radiologists without breast ultrasound expertise at secondary or rural hospitals in the differentiation of benign and malignant breast lesions measuring up to 2.0 cm on ultrasound. METHODS. This prospective study included patients scheduled to undergo biopsy or surgical resection at any of eight participating secondary or rural hospitals in China of a breast lesion classified as BI-RADS category 3-5 on prior breast ultrasound from November 2021 to September 2022. Patients underwent an additional investigational breast ultrasound, performed and interpreted by a radiologist without breast ultrasound expertise (hybrid body/breast radiologists, either who lacked breast imaging subspecialty training or for whom the number of breast ultrasounds performed annually accounted for less than 10% of all ultrasounds performed annually by the radiologist), who assigned a BI-RADS category. CAD results were used to upgrade reader-assigned BI-RADS category 3 lesions to category 4A and to downgrade reader-assigned BI-RADS category 4A lesions to category 3. Histologic results of biopsy or resection served as the reference standard. RESULTS. The study included 313 patients (mean age, 47.0 ± 14.0 years) with 313 breast lesions (102 malignant, 211 benign). Of BI-RADS category 3 lesions, 6.0% (6/100) were upgraded by CAD to category 4A, of which 16.7% (1/6) were malignant. Of category 4A lesions, 79.1% (87/110) were downgraded by CAD to category 3, of which 4.6% (4/87) were malignant. Diagnostic performance was significantly better after application of CAD, in comparison with before application of CAD, in terms of accuracy (86.6% vs 62.6%, p < .001), specificity (82.9% vs 46.0%, p < .001), and PPV (72.7% vs 46.5%, p < .001) but not significantly different in terms of sensitivity (94.1% vs 97.1%, p = .38) or NPV (96.7% vs 97.0%, p > .99). CONCLUSION. CAD significantly improved radiologists' diagnostic performance, showing particular potential to reduce the frequency of benign breast biopsies. CLINICAL IMPACT. The findings indicate the ability of CAD to improve patient care in settings with incomplete access to breast imaging expertise.

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is the most prevalent sleep disturbance that affects approximately 936 million people worldwide and leads to extensively increased incidence of cardiovascular disease, metabolic syndrome, neurological disorders, and traffic accidents. Severe OSA patients suffer a significantly higher risk of complications and worse comorbidity outcomes. Notwithstanding, with inadequate access to contact diagnosis based on polysomnography (PSG), numerous patients with severe sleep apnea have not been diagnosed, especially during the pandemic. Moreover, how the T cell immunity is impaired in OSA remains largely unknown. Methods: We primarily investigated the T cell receptor (TCR) repertoires of 50 patients with severe OSA, 23 patients with mild-to-moderate OSA, 23 patients without OSA, and 157 healthy individuals, from their peripheral blood. Firstly, we compared the clinical characteristics, blood cell counts, the ratio of neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and CD4+/CD8+T cell count between groups. Then, we compared the diversity, clonotypes, unique VJ alleles in patients with different disease severity. Furthermore, by identifying a series of disease-associated amino acid sequences, we employed a repeated hold-out machine learning strategy to explore the optimal algorithm for calculating the TCR repertoire characteristic Index (OSA-TCI). We further confirmed its relation with clinical features by linear regression analysis. Moreover, in followup of severe OSA patients who accepted adherent non-invasive ventilation, we assessed the changes of TCR repertoires, OSA-TCI, ESS, NLR, PLR, and CD4+/CD8+T after therapy. Results: We found an unexpected increase in diversity and clonotypes in the TCR repertoire of OSA patients. Furthermore, we successfully developed a novel indicator termed OSA-TCI to summarize the unique repertoire alteration, which provided 90% of sensitivity and 87% of specificity in distinguishing severe OSA. In rationalization, OSA-TCI was found correlated to AHI, BMI, hemoglobin, N1, N2 percentage of sleep, snoring, smoking and lowest oxygen saturation, but only independently related to AHI (R = 0.603) and smoking (R = 0.22). Finally, we observed OSA-TCI in the eight severe patients decreased significantly after home noninvasive ventilation for three months during follow-up, consistently in line with the TCR repertoire improvement. In contrast, NLR, PLR, and the ratio of CD4+/CD8+T cell count were found useless to diagnose and therapeutic surveillance of severe OSA. Conclusions: Our study is the first to unveil the TCR repertoire alteration in OSA, indicates possible insidious autoimmune mechanisms underlying OSA, and suggests that TCR repertoires serve as a convenient peripheral blood biomarker for OSA assessment without long-time contact and facility/instrument occupation. It may shed light on future diagnostic, immunological, pathophysiological, and prognostic research on OSA.

Diabetic endothelial microangiopathy and pulmonary dysfunction.

Type 2 diabetes mellitus (T2DM) is a widespread metabolic condition with a high global morbidity and mortality rate that affects the whole body. Their primary consequences are mostly caused by the macrovascular and microvascular bed degradation brought on by metabolic, hemodynamic, and inflammatory variables. However, research in recent years has expanded the target organ in T2DM to include the lung. Inflammatory lung diseases also impose a severe financial burden on global healthcare. T2DM has long been recognized as a significant comorbidity that influences the course of various respiratory disorders and their disease progress. The pathogenesis of the glycemic metabolic problem and endothelial microangiopathy of the respiratory disorders have garnered more attention lately, indicating that the two ailments have a shared history. This review aims to outline the connection between T2DM related endothelial cell dysfunction and concomitant respiratory diseases, including Coronavirus disease 2019 (COVID-19), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

The deep origin of ground fissures in the Kenya Rift Valley.

Intense volcanic and geothermal activities characterize the Great Rift Valley of East Africa. Ground fissure disasters of the Great Rift Valley have garnered increasing attention in recent years. Through field investigations, trenching, geophysical exploration, gas sampling and analysis, we determined the distribution and origin of 22 ground fissures within the Kedong Basin of the Central Kenya Rift. These ground fissures caused varying degrees of damage to roads, culverts, railways, and communities. Trenching and geophysical exploration have shown that ground fissures in sediments are connected to rock fractures with gas escaping. The gases expelled from the rock fractures contained methane and SO2, which were absent in the normal atmosphere, and 3He/4He ratios in gases measured further indicated that the volatiles were derived from the mantle, suggesting that these rock fractures extended deep into the underlying bedrock. Spatial correlations with rock fractures demonstrate the deep origin of these ground fissures, which are associated with active rifting, plate separation, and volcanism. The ground fissures are formed due to movement on the deeper rock fractures, and then the gas escapes through the fissures. Determining the unusual origin of these ground fissures can not only guide infrastructure development and urban planning but also contribute to the safety of local communities.

IL-1ß promotes IL-17A production of ILC3s to aggravate neutrophilic airway inflammation in mice.

IL-17A-producing group 3 innate lymphoid cells (ILC3s) have been found to participate in the development of various phenotypes of asthma, however, little is known about how ILC3s mediate neutrophilic airway inflammation. Elevated IL-1ß has been reported in neutrophilic asthma (NA) and IL-1ß receptor is highly expressed on lung ILC3s. Therefore, we hypothesize that IL-1ß aggravates neutrophilic airway inflammation via provoking IL-17A-producing ILC3s. We sought to determine the pathological roles of the IL-1ß-ILC3-IL-17A axis in neutrophilic airway inflammation. Lung ILC subsets were measured in eosinophilic asthma (ovalbumin [OVA]/Alum) and NA (OVA/lipopolysaccharides [LPS]) murine models. Rag2-/- (lacking adaptive immunity), RORc-/- (lacking transcription factor RORγt), Rag2-/- RORc-/- (lacking adaptive immunity and ILC3s), and ILCs depletion mice were used to verify the roles of ILC3s in neutrophilic airway inflammation by measurement of CXCL-1, IL-17A, IL-22 and neutrophil counts in bronchoalveolar lavage fluid (BALF), detection of Muc5ac in lung tissues, and quantification of IL-17A-producing ILC3s after treatment of anti-IL-17A or recombinant IL-1ß (rIL-1ß) and its monoclonal antibody. NLRP3, Caspase 1 and their induction of IL-1ß were detected in lung tissues of OVA/LPS-induced mice. The OVA/LPS model was characterized by an enrichment of airway neutrophilia, lung RORγt+ ILC3s and Th17 cytokines (IL-17A and IL-22) and neutrophilic chemokine C-X-C motif (chemokine) ligand 1 (CXCL-1), compared to the phenotypic features of airway eosinophilia, GATA3+ ILC2s and type-2 cytokines in OVA/Alum model. The concentration of CXCL-1 and neutrophil counts in BALF were decreased by anti-IL-17A. RORγt deficiency led to a decrease in IL-17A and CXCL-1 levels and neutrophil counts in BALF. ILC depletion in Rag2-/- mice ameliorated OVA/LPS-induced IL-17A, IL-22, CXCL-1 and airway neutrophil counts. IL-17A-producing ILCs and BALF neutrophil counts were significantly lower in Rag2-/- RORc-/- mice than those in Rag2-/- mice. IL-1ß was highly expressed in BALF and bronchial epithelial cells (BECs) in OVA/LPS model, and administration of rIL-1ß substantially aggravated airway inflammation and promoted upregulation of RORγt+ and IL-17A-producing lung ILC3s, which were reversed by anti-IL-1ß. NLRP3 and Caspase 1 expressions were enhanced by OVA/LPS, and their inhibitors abolished the OVA/LPS-induced IL-1ß in BECs. ILC3s play a pathogenic role in the pathogenesis of NA, which is triggered by IL-1ß via promoting IL-17A production of lung ILC3s.

Multiple rectal neuroendocrine tumors: An analysis of 15 cases and literature review.

Multiple neuroendocrine tumors (M-NETs) are rare in the rectum and there is no consensus on their characteristics and treatments. Here, we report 15 cases of rectal M-NETs and review the previous literature. We discuss the clinical characteristics, endoscopic features and pathological features of rectal M-NETs, aiming to analyze the treatments and follow-up strategies in combination with these characteristics. We retrospectively reviewed and analyzed the data of 15 patients with rectal M-NETs who were diagnosed and treated at Beijing Friendship Hospital, Capital Medical University. Their clinical data, endoscopic findings, pathological features and treatments were analyzed. Follow-up evaluations and literature review were performed. In all, 14 male (93.3%) and 1 female (6.7%) were recruited. The average age at diagnosis was 55.7 years. The clinical manifestations include asymptomatic in 9 patients (60.0%), defecation habits changes in 2 patients (13.3%), anal distension in 2 patients (13.3%), and abdominal distension in 2 patient (13.3%). The largest tumor diameter ≤10mm was found in 13 patients (86.7%) and >10mm in 2 patients (13.3%). All of the lesions originated from the mucous or submucosa layer. WHO grades were all NET G1. The number of tumors diagnosed by pathology in 13 patients was consistent with that observed by endoscopy, while more lesions were observed by pathology than endoscopy in two patients. Lymph node metastasis occurred in 1 patient (6.7%), and vascular or lymphatic invasion occurred in 9 patients (60.0%). Among the 13 patients with the largest tumor diameter being ≤10mm, lymphovascular invasion occurred in 8 patients (61.5%). And among the 2 patients with the largest tumor diameter of >10mm, lymphovascular invasion occurred in 1 patient (50.0%). 14 patients underwent endoscopic resection and 1 underwent surgical excision. Postoperative follow-up was achieved in 13 patients and no recurrence or metastasis was found. The true number of rectal M-NETs may be more than seen under endoscopy. Rectal M-NETs is associated with a high risk of metastasis; therefore, treatment and surveillance strategies should be more radical than single lesion.

Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

Flower-like molybdenum disulfide decorated ZIF-8-derived nitrogen-doped dodecahedral carbon for electro-catalytic degradation of phenol.

In this work, flower-like molybdenum disulfide was constructed on the surface of ZIF-8-derived nitrogen-doped dodecahedral carbon (ZNC) for the electrocatalytic degradation of phenol. The flower-like nanostructure of MoS2@ZNC contributed to the exposure of more edge-active sites of MoS2. At the same time, Mo4+ and Mo6+ co-existed in MoS2@ZNC, which promoted the generation of H2O2 and •OH, and improved the catalytic activity of composite materials. In addition, electrochemical performance analysis showed that MoS2 loaded on the surface of ZNC significantly improved the redox capacity of the material, and the composite ratio of MoS2 and ZNC affected the structure and properties of MoS2@ZNC composites. Moreover, the electrochemical performance of prepared MoS2@ZNC was evaluated by the generation of hydroxyl (•OH) and the degradation efficiency of phenol. The results showed that MoS2@ZNC-2 had an excellent phenol degradation efficiency (98.8%) and COD removal efficiency (86.8%) within 120 min. Furthermore, MoS2@ZNC cathode still maintained good performance after being experimented with 20 times, indicated the excellent stability of MoS2@ZNC.

Asthma Management Using the Mobile Asthma Evaluation and Management System in China.

PURPOSE: As stated in the Global Initiative for Asthma, there are still some asthmatic patients who have not achieved asthma control. Mobile is a useful tool for asthma management. We aimed to compare the advantages of mobile management with traditional management in improving adherence and control of asthma. METHODS: In this prospective, multicentre, randomized, controlled and parallel-group study, we enrolled patients with poor adherence and uncontrolled asthma at 32 hospitals in 28 provinces in China. Patients were randomly assigned to the mobile management or traditional management groups for 12 months. The primary endpoint was the proportion of patients with good adherence (Medication Adherence Report Scale for Asthma [MARS-A] score ≥ 45) for 6 months. This study is registered at ClinicalTrials.gov (NCT02917174). RESULTS: Between April 2017 and April 2018, 923 patients were eligible for randomization (mobile group, n = 461; traditional group, n = 462). Dropout was 84 (18.2%) in the mobile management group and 113 (24.4%) patients in the traditional management group. The proportion of patients with good adherence was significantly higher in the mobile management group than in the traditional management group (66.0% vs. 58.99%, P = 0.048). The mobile management group showed higher mean MARS-A score (at 1, 6, 9, and 12 months) and asthma control test scores (at 6 and 9 months), and lower total lost rate to follow-up within 12 months than the traditional management group. CONCLUSIONS: Mobile asthma management can improve adherence and asthma control compared to traditional management. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02917174.

A pilot study of differential gene expressions in patients with cough variant asthma and classic bronchial asthma.

BACKGROUND: Despite extensive exploration of asthma, the mechanism of asthma has not been fully elucidated. Cough variant asthma (CVA) is considered as precursor to classical asthma (CA). Comparative study between CA and CVA may be helpful in further understanding the pathogenesis of asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from CVA, CA and healthy adults. Each group consisted of five cases. Total RNA was extracted from the PBMCs. Agilent 4 × 44 K human genome oligo microarray was used to detect whole genome expression. Allogeneic clustering, Gene Ontology and KEGG analysis were performed to investigate differentially expressed genes (DEGs). Then, ten candidate genes were screened and verified by real-time PCR. RESULTS: Gene expressions were significantly different among the three groups, with 202 DEGs between the CA and the CVA groups. The Gene Ontology analysis suggested that the DEGs were significantly enriched in 'histone H4-K20 demethylation' and 'antigen processing and presentation of endogenous antigens'. HDC, EGR1, DEFA4, LTF, G0S2, IL4, TFF3, CTSG, FCER1A and CAMP were selected as candidate genes. However, the results of real-time PCR showed that the expression levels of FCER1A, IL4 and HDC in the cough variant asthma group were significantly different from those in the other two groups (p < 0.05). CONCLUSIONS: The pathogenesis of CVA and CA may be related to genes such as FCER1A, HDC and IL4. Further studies incorporating a larger sample size should be conducted to find more candidate genes and mechanisms.

Children and Adolescents' Psychological Well-Being Became Worse in Heavily Hit Chinese Provinces during the COVID-19 Epidemic.

In light of the novel coronavirus's (COVID-19's) threat to public health worldwide, we sought to elucidate COVID-19's impacts on the mental health of children and adolescents in China. Through online self-report questionnaires, we aimed to discover the psychological effects of the pandemic and its associated risk factors for developing mental health symptoms in young people. We disseminated a mental health survey through online social media, WeChat, and QQ in the five Chinese provinces with the most confirmed cases of COVID-19 during the late stage of the country-wide lockdown. We used a self-made questionnaire that queried children and adolescents aged 6 to 18 on demographic information, psychological status, and other lifestyle and COVID-related variables. A total of 17,740 children and adolescents with valid survey data participated in the study. 10,022 (56.5%), 11,611 (65.5%), 10,697 (60.3%), 6868 (38.7%), and 6225 (35.1%) participants presented, respectively, more depressive, anxious, compulsive, inattentive, and sleep-related problems compared to before the outbreak of COVID-19. High school students reported a greater change in depression and anxiety than did middle school and primary school students. Despite the fact that very few children (0.1%) or their family members (0.1%) contracted the virus in this study, the psychological impact of the pandemic was clearly profound. Fathers' anxiety appeared to have the strongest influence on a children's psychological symptoms, explaining about 33% of variation in the child's overall symptoms. Other factors only explained less than 2% of the variance in symptoms once parents' anxiety was accounted for. The spread of COVID-19 significantly influenced the psychological state of children and adolescents in participants' view. It is clear that children and adolescents, particularly older adolescents, need mental health support during the pandemic. The risk factors we uncovered suggest that reducing fathers' anxiety is particularly critical to addressing young people's mental health disorders in this time.