Using targeted second-generation sequencing technique to guide clinical diagnosis and the effect of medication on the therapeutic effect and prognosis of respiratory tract infection in children: An observational study.

To explore the effect of targeted second-generation sequencing technique to guide clinical diagnosis and medication on the therapeutic effect and prognosis of respiratory tract infection (RTI) in children. During January 2021 to June 2022, 320 children with RTI cured were selected in our hospital as the object of this retrospective study. The control group accepted empirical broad-spectrum antibacterial therapy and the observation group accepted targeted second-generation sequencing technique to guide diagnosis and medication. The therapeutic effect, improvement time of clinical symptom index, laboratory-related index, level of inflammatory factors, incidence of complications, and parents' treatment satisfaction were compared. The observation group was considerably more efficacious (91.25%) versus the controlled group (72.50%). The duration of enhancement of fever, nasal congestion, tonsillar congestion, and cough symptoms was shorter in the observation group (P < .05). Serum levels of iron, IgA, IgG as well as IgM were substantially elevated in the observation group. The levels of IL-4 and IL-10 were markedly reduced in the observation group after treatment. The prevalence of complications was considerably below that of the comparison group (21.25%) in the observation group (8.75%). Parental satisfaction with therapy was markedly higher in the observation group (92.50%) than in the control group (66.25%). The application of targeted second-generation sequencing technology to guide clinical diagnosis and drug use can elevate the RTIs efficacy and prognosis in childhood. Targeted second-generation sequencing can achieve precise treatment, reduce drug resistance of drug-resistant strains, and improve the efficacy. It has high promotion and application value.

Effects of Chemical Composition and Cross-Linking Degree on the Thermo-Mechanical Properties of Bio-Based Thermosetting Resins: A Molecular Dynamics Simulation Study.

Bio-based epoxy resins have received significant attention in terms of concerns regarding carbon emission. Epoxidized soybean oil (ESO) derived from sustainable feedstock has been widely used to blend with traditional diglycidyl ether of bisphenol-A (DGEBA) to replace some of the petroleum-based components. In this work, molecular dynamics (MD) simulations were applied to track the network formation and predict the performance of methyl hexahydrophthalic anhydride (MHHPA)-cured ESO/DGEBA blend systems. The effects of ESO content and cross-linking degree on the mass density, volumetric shrinkage, glass transition temperature (Tg), coefficient of thermal expansion (CTE), Young's modulus, yield strength, and Poisson's ratio of the epoxy resin were systematically investigated. The results show that systems with high ESO content achieve gelation at low cross-linking degree. The Tg value, Young's modulus, and yield strength increase with the increase in cross-linking degree, but the CTE at the glassy state and Poisson's ratio decrease. The comparison results between the simulated and experimental data demonstrated that the MD simulations can accurately predict the thermal and mechanical properties of ESO-based thermosets. This study gains insight into the variation in thermo-mechanical properties of anhydride-cured ESO/DGEBA-based epoxy resins during the cross-linking process and provides a rational strategy for optimizing bio-based epoxy resins.

Machine Learning Analysis Classifies Patients with Primary Angle-Closure Glaucoma Using Abnormal Brain White Matter Function.

Objective: Primary angle-closure glaucoma (PACG) is a globally prevalent, irreversible eye disease leading to blindness. Previous neuroimaging studies demonstrated that PACG patients were associated with gray matter function changes. However, whether the white matter(WM) function changes in PACG patients remains unknown. The purpose of the study is to investigate WM function changes in the PACG patients. Methods: In total, 40 PACG patients and 40 well-matched HCs participated in our study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We compared between-group differences between PACG patients and HC in the WM function using amplitude of low-frequency fluctuations (ALFF). In addition, the SVM method was applied to the construction of the PACG classification model. Results: Compared with the HC group, ALFF was attenuated in right posterior thalamic radiation (include optic radiation), splenium of corpus callosum, and left tapetum in the PACG group, the results are statistically significant (GRF correction, voxel-level P < 0.001, cluster-level P < 0.05). Furthermore, the SVM classification had an accuracy of 80.0% and an area under the curve (AUC) of 0.86 for distinguishing patients with PACG from HC. Conclusion: The findings of our study uncover abnormal WM functional alterations in PACG patients and mainly involves vision-related regions. These findings provide new insights into widespread brain damage in PACG from an alternative WM functional perspective.

Altered functional connectivity between the default mode network in primary angle-closure glaucoma patients.

Previous studies have recognized glaucoma as a neurodegenerative disease that causes extensive brain damage and is closely associated with cognitive function. In this study, we employed functional MRI to examine the intrinsic functional connectivity patterns of the default mode network (DMN) in patients diagnosed with primary angle-closure glaucoma (PACG), exploring its association with cognitive dysfunction. A total of 34 patients diagnosed with PACG and 34 healthy controls (HC), who were matched in terms of sex, age, and education, were included in the control group. The posterior cingulate cortex (PCC) was selected as the region of interest to examine functional connectivity alterations. Compared with the HC group, functional connectivity was attenuated in left anterior cingulum cortex and left paracentral lobule between with PCC in the PACG group, the results are statistically significant. Our study revealed that patients with PACG exhibit weakened functional connectivity within the DMN. This finding suggests the presence of a neurological mechanism that is associated with both visual dysfunction and cognitive impairments in PACG patients. Furthermore, our study provides neuroimaging evidence that can aid in the exploration of spontaneous neurological alterations and facilitate a deeper investigation of alterations in the visual conduction pathways of PACG patients.

Parathyroid hormone enhances the therapeutic effect of mesenchymal stem cells on temporomandibular joint osteoarthritis in rats.

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the joint, which is characterized by injury to the articular cartilage, as well as changes in the synovial and subchondral bone. TMJOA has a high incidence rate, without any effective treatment. Despite the therapeutic potential of mesenchymal stem cells (MSCs) in various diseases, their efficacy in treating TMJOA is constrained by the local hypoxic conditions and elevated reactive oxygen species (ROS) environment within the damaged temporomandibular joint. In recent years, many studies have reported that parathyroid hormone (PTH) can effectively treat TMJOA, and has an important impact on MSC differentiation. Therefore, we hypothesized that PTH may influence the potential of MSCs, thereby improving their therapeutic effect on TMJOA. METHODS: First, we isolated and cultured rat bone marrow MSCs, and evaluated their proliferation and differentiation after adding PTH. Next, the in vitro environment of hypoxia and high ROS was established by hypoxia condition and H2O2 treatment, and the resistance of PTH-treated MSCs to hypoxia and ROS was subsequently investigated. Finally, PTH-treated MSCs were used to treat TMJOA in a rat model to evaluate the efficacy of PTH. RESULTS: PTH enhanced the proliferation ability of MSCs, promoted the osteogenic differentiation of MSCs, and improved the tolerance of MSCs to hypoxia and ROS. Finally, the therapeutic effect of PTH-treated MSCs on TMJOA was significantly improved. CONCLUSION: PTH enhances the therapeutic effect of MSCs on TMJOA in rats.

Huashi baidu granule in the treatment of pediatric patients with mild coronavirus disease 2019: A single-center, open-label, parallel-group randomized controlled clinical trial.

Background: Since late February 2022, a wave of coronavirus disease 2019 (COVID-19) mainly caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly appeared in Shanghai, China. Traditional Chinese medicine treatment is recommended for pediatric patients; however, the safety and efficacy remain to be confirmed. We conducted a single-center, open-label, parallel-group randomized controlled trial to assess the efficacy and safety of a Chinese herb compound, Huashi Baidu granule (HSBDG) in pediatric patients with laboratory-confirmed mild COVID-19. Methods: 108 recruited children (aged 3-18 years) with laboratory-confirmed mild COVID-19 were randomly allocated 2:1 to receive oral HSBDG for five consecutive days (intervention group) and to receive compound pholcodine oral solution for five consecutive days (control group). The negative conversion time of SARS-CoV-2 nucleic acid and symptom scores were recorded. Results: The median negative conversion time of SARS-CoV-2 nucleic acid was significantly shorter in the intervention group than in the control group (median days [interquartile range (IQR)]: 3 [3-5] vs. 5 [3-6]; p = 0.047). The median total symptom score on day 3 was significantly lower in the intervention group than in the control group (median total symptom score [IQR]: 1 [0-2] vs. 2 [0-3]; p = 0.036). There was no significant differences in the frequency of antibiotic use and side effects between the two groups. Conclusion: HSBDG is a safe, effective oral Chinese herbal compound granule, which shows a good performance within the Omicron wave among pediatric patients.

FOXF1 attenuates TGF­ß1­induced bronchial epithelial cell injury by inhibiting CDH11­mediated Wnt/ß­catenin signaling.

Forkhead box F1 (FOXF1) has been reported to be associated with lung development. However, the role of FOXF1 in asthma is still not fully understood. In the present study, the biological role and the potential mechanism of FOXF1 was explored in transforming growth factor ß1 (TGF-ß1)-induced bronchial epithelial cell injury. Reverse transcription-quantitative PCR and western blotting were performed to detect the expression levels of FOXF1 and cadherin (CDH) 11 in TGF-ß1-induced bronchial epithelial cells. Proliferation, apoptosis and inflammation were assessed using Cell Counting Kit-8 assay, flow cytometry, western blotting and ELISA. Fibrosis and epithelial-mesenchymal transition (EMT) were evaluated using immunofluorescence and western blotting. The expression levels of the proteins involved in the Wnt/ß-catenin pathway were detected by western blotting. The results indicated that FOXF1 expression was downregulated, while CDH11 expression was upregulated in TGF-ß1-treated BEAS-2B cells. FOXF1 overexpression promoted proliferation, inhibited induction of apoptosis and suppressed the inflammatory response of BEAS-2B cells exposed to TGF-ß1. In addition, FOXF1 overexpression restrained TGF-ß1-induced bronchial epithelial fibrosis and EMT and inhibited the activation of the Wnt/ß-catenin pathway. CDH11 overexpression reversed the effects of FOXF1 overexpression on proliferation, apoptosis, fibrosis, EMT and inflammation by regulating the Wnt/ß-catenin pathway. Collectively, the results of the present study suggested that FOXF1 regulated TGF-ß1-induced BEAS-2B cell injury by inhibiting CDH11-mediated Wnt/ß-catenin signaling. This may provide a novel therapeutic strategy for the treatment of asthma.

Allergic diseases aggravate the symptoms of SARS-CoV-2 infection in China.

Background: The relationship between allergic diseases and the adverse outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a subject of controversy. This study aimed to investigate the association between allergic diseases and the incidence and severity of symptoms in SARS-CoV-2 infection. Methods: Clinical data of individuals, including children and their parents, infected with SARS-CoV-2 from December 2022 to January 2023 in China were retrospectively analyzed. The data were collected through questionnaires. Statistical analysis, including chi-squared tests, nonparametric analysis, one-way ANOVA, and logistic regression analysis, was used to examine the relationship between allergic diseases, prior medication, and the symptoms of SARS-CoV-2 infection. Results: There were 3,517 adults and 3,372 children with SARS-CoV-2 infection included in the study. Fever was found to occur at similar rates in children (86.5%) and adults (86.8%). However, other symptoms related to respiratory issues (such as cough and sore throat), neurological symptoms (headache, loss of smell, and loss of taste), and systemic symptoms (muscle soreness and weakness) were observed more frequently in adults (P < 0.001). Additionally, adults exhibited higher overall symptom scores, indicating greater severity. Allergic diseases were found to be associated with the incidence of certain SARS-CoV-2 infection symptoms in both children and adults. Specifically, children with allergic rhinitis (AR) were observed to be more susceptible to upper respiratory symptoms (OR: 1.320, 95% CI: 1.081-1.611, P = 0.006), while asthma patients were found to be more susceptible to severe respiratory symptoms (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). Similar patterns were identified in adults. Furthermore, AR was also suggested to be a risk factor for symptom severity in both children (OR: 1.704, 95% CI: 1.314-2.209, P < 0.001) and adults (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). However, prior medication for allergic diseases did not exhibit a preventive effect on SARS-CoV-2 infection symptoms. Conclusions: Both children and adults with allergic diseases were found to be more prone to experiencing symptoms of SARS-CoV-2 infection, and these symptoms tended to be more severe.

Bivalirudin exerts antiviral activity against respiratory syncytial virus-induced lung infections in neonatal mice.

Respiratory syncytial virus (RSV) is the most common cause of small airways inflammation in the lungs (bronchiolitis) in neonates and immunocompromised adults. The deregulation of cellular and plasma components leads to increased morbidity and mortality. The activation of the clotting cascade plays a key role in the progression of disease severity during viral infection. The current investigation studied the effect of bivalirudin (BR) on the progression and cellular effects of RSV-induced infection in the neonatal mice model. Mice (5-7 days old) were inoculated intranasally with RSV with or without BR administration (2 mg kg-1 day-1, i.v.) for 2 weeks. Tissue histopathology, inflammatory signalling genes such as TLR, and cytokines were analyzed. The results showed pneumocytes exhibiting nuclear pyknosis, cellular infiltration in lung tissue and increased lung titers in RSV-infected mice compared to the control. Furthermore, RSV-infected mice demonstrated altered clotting parameters such as D-dimer, soluble thrombomodulin, and increased inflammatory cytokines IL-5, 6, IFN-γ, IL-13, and CXCL1. Additionally, the mRNA expression analysis displayed increased levels of IL-33, TLR3, and TLR7 genes in RSV-infected lung tissue. Further, to delineate the role of micro RNAs, the qRT-PCR analysis was done, and the results displayed an increase in miR-136, miR-30b, and let-7i. At the same time, the down-regulated expression of miR-221 in RSV-infected mice compared to the control. BR treatment reduced the cellular infiltration with reduced inflammatory cytokines and normalized clotting indices. Thus, the study shows that RSV infection induces specific changes in lung tissue and the clotting related signalling mechanism. Additionally, BR treatment significantly reduces bronchiolitis and prevents the severity of the infections suggesting that BR can possibly be used to reduce the viral-mediated infections in neonates.

Facile Synthesis of Thermoplastic Polyamide Elastomers Based on Amorphous Polyetheramine with Damping Performance.

Novel thermoplastic polyamide elastomers (TPAEs) consisting of long-chain semicrystalline polyamide 1212 (PA1212) and amorphous polyetheramine were synthesized via one-pot melt polycondensation. The method provides accessible routes to prepare TPAEs with a high tolerance of compatibility between polyamide and polyether oligomers compared with the traditional two-step method. These TPAEs with 10 wt % to 76 wt % of soft content were obtained by reaction of dodecanedioic acid, 1,12-dodecanediamine, and poly(propylene glycol) (PPG) diamine. The structure-property relationships of TPAEs were systematically studied. The chemical structure and the morphologic analyses have revealed that microphase separation occurs in the amorphous region. The TPAEs that have long-chain PPG segments consist of a crystalline polyamide domain, amorphous polyamide-rich domain, and amorphous polyetheramine-rich domain, while the ones containing short-chain PPG segments comprise of a crystalline polyamide domain and miscible amorphous polyamide phase and amorphous polyetheramine phase due to the compatibility between short-chain polyetheramine and amorphous polyamide. These novel TPAEs show good damping performance at low temperature, especially the TPAEs that incorporated 76 wt % and 62 wt % of PPG diamine. The TPAEs exhibit high elastic properties and low residual strain at room temperature. They are lightweight with density between 1.01 and 1.03 g/cm3. The long-chain TPAEs have well-balanced properties of low density, high elastic return, and high shock-absorbing ability. This work provides a route to expand TPAEs to damping materials with special application for sports equipment used in extremely cold conditions such as ski boots.

Age-specific risk factors of severe pneumonia among pediatric patients hospitalized with community-acquired pneumonia.

BACKGROUND: Risk factors that predispose the development of severe community-acquired pneumonia (CAP) among pediatric CAP patients of different age ranges are yet to be identified. METHODS: We retrospectively analyzed pediatric in-patients (< 6 years old) diagnosed with CAP in our hospital. We subdivided patients into four age groups (< 6 months, 6 months-1 year, 1-2 years, and 2-6 years). Their medical records, including demographic information, clinical features, laboratory findings, and chest radiographic reports, were reviewed and collected for further analysis. Univariate logistic regression analysis and stepwise regression analysis were applied to identify risk factors associated with severe CAP and ICU admission for overall patients and age-stratified subgroups. RESULTS: A total of 20,174 cases were initially included. Among them, 3309 (16.40%) cases were identified as severe CAP, and 2824 (14.00%) cases required ICU admission. Potential risk factors for severe CAP and ICU admission identified by univariate analysis included younger age, rural residency, premature birth, low birth weight (LBW), formula feeding, congenital heart disease (CHD), history of pneumonia or neonatal jaundice, patients with other health issues, certain symptoms (manifesting wheezing, dyspnea, cyanosis, but have no cough or fever), abnormal laboratory findings (abnormal levels of white blood cells, albumin, and C-reactive protein and RSV infection), and chest X-ray (odds ratio [OR] > 1 for all). CHD, low albumin, proteinuria, abnormal chest x-ray were independent risks factors across different age groups, whereas birth or feeding history, history of pneumonia, cyanosis or dyspnea on admission, and RSV infection were independent risk factors for only younger kids (< 1 year), and wheezing was an independent risk factor only for older children (2-5 years old). CONCLUSIONS: Risk factors predicting disease severity among children hospitalized with CAP vary with age. Risk factor stratification of pediatric CAP based on age-specific risk factors can better guide clinical practice. TRIAL REGISTRATION: This study has been registered in China, with the registration number being ChiCTR2000033019 .

Boron Quantum Dots for Photoacoustic Imaging-Guided Photothermal Therapy.

Photothermal therapy is a new type of tumor therapy with great potential. An ideal photothermal therapy agent should have high photothermal conversion effect, low biological toxicity, and degradability. The development of novel photothermal therapy agents with these properties is of great demand. In this study, we synthesized boron quantum dots (BQDs) with an ultrasmall hydrodynamic diameter. Both in vitro and in vivo studies show that the as-synthesized BQDs have good biological safety, high photoacoustic imaging performance, and photothermal conversion ability, which can be used for photoacoustic imaging-guided photothermal agents for tumor treatment. Our investigations confirm that the BQDs hold great promise in tumor theranostic applications.

Nucleoporin 107 facilitates the nuclear export of Scn5a mRNA to regulate cardiac bioelectricity.

Nucleoporins (Nups) are known to be functional in nucleo-cytoplasmic transport, but the roles of nucleoporins in nonproliferating cells, such as cardiac myocytes, are still poorly understood. In this study, we report that Nup107 regulates cardiac bioelectricity by controlling the nucleo-cytoplasmic trafficking of Scn5a mRNA. Overexpression of Nup107 induced the protein expression of Scn5a rather than that of other ion channels, with no effects of their mRNA levels. The analysis for the protein production demonstrated Nup107-facilitated transport of Scn5a mRNA. Using RIP-PCR and luciferase assay, we found that the 5'-UTR of Scn5a mRNA was not involved in the interaction, whereas the spatial interaction between Nup107 protein and Scn5a mRNA was formed when Scn5a mRNA passing through the nuclear pore. Functionally, Nup107 overexpression in neonatal rat ventricle myocytes significantly increased the currents of Scn5a-encoded INa channel. Moreover, the close correlation between Nup107 and Nav1.5 protein expression was observed in cardiomycytes and heart tissues subjected to hypoxia and ischaemic insults, suggesting a fast regulation of Nup107 on Nav1.5 channel in cardiac myocytes in a posttranscriptional manner. These findings may provide insights into the emergent control of cardiac electrophysiology through Nup-mediated modulation of ion channels.