Predictive Value of Impulse Oscillometry Combined with Fractional Expiratory Nitric Oxide Test for Asthma in Preschool Children.

Objective: Prediction of asthma in preschool children is challenging and lacks objective indicators. The aim is to observe and analyze the variances between impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in preschool children with wheezing, establish a joint prediction model, and explore the diagnostic value of combining IOS with FeNO in diagnosing asthma among preschool children. Patients and methods: This study enrolled children aged 3-6 years with wheezing between June 2021 and June 2022. They were categorized as asthmatic (n=104) or non-asthmatic (n=109) after a 1-year follow-up. Clinical data, along with IOS and FeNO measurements from both groups, underwent univariate regression and multiple regression analyses to identify predictive factors and develop the most accurate model. The prediction model was built using the stepwise (stepAIC) method. The receiver operating characteristic curve (ROC), calibration curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) were employed to validate and assess the model. Results: During univariate analysis, a history of allergic rhinitis, a history of eczema or atopic dermatitis, and measures including FeNO, R5, X5, R20, Fres, and R5-R20 were found to be associated with asthma diagnosis. Subsequent multivariate analysis revealed elevated FeNO, R5, and X5 as independent risk factors. The stepAIC method selected five factors (history of allergic rhinitis, history of eczema or atopic dermatitis, FeNO, R5, X5) and established a prediction model. The combined model achieved an AUROC of 0.94, with a sensitivity of 0.89 and specificity of 0.88, surpassing that of individual factors. Calibration plots and the HL test confirmed satisfactory accuracy. Conclusion: This study has developed a prediction model based on five factors, potentially aiding clinicians in early identification of asthma risk among preschool children.

USP5 negatively regulates the activation of NLRP3 inflammasomes and participates in the pathological and physiological processes of Sjogren's syndrome.

OBJECTIVE: The current treatment and mechanism of Sjogren's syndrome (SS) are unclear. The purpose of the present study was to potential molecular mechanisms of SS. METHODS: Immunohistochemical and immunofluorescence techniques reveal the targets and therapeutic approaches of SS. RESULTS: We found through molecular biology techniques such as immunoblotting and immunoprecipitation that USP5 is a novel regulator of NLRP3 involvement in the pathological process of SS. USP5 was significantly downregulated in submandibular gland tissue of SS. Meanwhile, it was found that USP5 is a negative regulator of NLRP3 via ubiquitination NLRP3. In addition, SalvianolicacidB (SaB), a natural USP5 agonist, can alleviate ss by regulating the USP5/NLRP3 signaling pathway. CONCLUSION: Therefore, this study provides a new mechanism for SS and also provides new therapeutic targets for treating SS.

Rutin alleviates Sjogren's syndrome via CaR/NLRP3/NF-κB signal pathway.

Sjogren's syndrome (SS) is an autoimmune disease. Its mechanism and treatment methods are unclear. The purpose of this study was to investigate the effects of rutin (Ru) on SS. Proteomics was used to detect differential proteins in the submandibular glands of normal mice and SS mice. Salivary secretion (SAS) and salivary gland index (SGI) were detected. Oxidative stress and inflammatory cytokine in submandibular glands were detected. The levels of NLRP3, ASC, Caspase-1, IL-1ß, and p-NF-κBp65 in submandibular gland tissues and submandibular gland cells of overexpressed calcium-sensing receptor (over-CaR) mice and overexpressed CaR primary submandibular gland cells (over-CaR-PSGs) were detected. In total, 327 differential proteins were identified in the submandibular gland tissues of SS mice compared to control mice. CaR was one of the most differential proteins and significantly increased compared to control mice. Ru could significantly increase SGI and SGI, and inhibit oxidative stress and inflammatory cytokine in submandibular glands. In addition, Ru was shown to further improve SS via regulation of the CaR/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/nuclear factor kappa-B (NF-κB) signal pathway. Overexpression of CaR counteracted partial activity of Ru. CaR may be an important target for the treatment of SS. In addition, Ru improved the SS via the CaR/NLRP3/NF-κB signal pathway. This study provides a basis for the treatments for SS.

Clinical significance of the expression levels of serum transforming growth factor-ß and CXC type chemokine ligand 13 in primary Sjogren's syndrome patients.

OBJECTIVE: The aim of this study was to investigate the expression levels of the serum transforming growth factor-ß1 (TGF-ß1) CXC type chemokine ligand 13 (CXCL13) in primary Sjogren's syndrome (pSS) patients and its correlation with disease severity. METHOD: Thirty patients with pSS admitted to Nanjing Traditional Chinese Medicine Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2021 to December 2022 were included as the pSS group, while 30 patients who underwent physical examination during the same period were included as the control group. The levels of TGF-ß1 and CXCL13 were detected. The diagnostic value of TGF-ß1 and CXCL13 for pSS was analyzed. Detection of serum TGF-ß1 and CXCL13 levels in pSS patients with different disease activities and lip gland pathological grading of pSS was done. We compared the correlation between TGF-ß1 and CXCL13 levels and disease activity and labial gland pathological grading in pSS patients. RESULT: The TGF-ß1 and CXCL13 levels in the pSS group were higher than those in the control group. The area under the receiver operating characteristic (ROC) curve (AUC) for TGF-ß1 and CXCL13 diagnosis of pSS was 0.790 (95% confidence interval (CI): 0.720~0.861) and 0.838 (95% CI: 0.778~0.898), respectively. The serum TGF-ß1 and CXCL13 levels of pSS patients significantly increase with the increase of disease activity and lip gland pathological grading. The TGF-ß1 and CXCL13 levels in pSS patients were positively correlated with disease activity and lip gland pathological grading. CONCLUSION: The levels of TGF-ß1 and CXCL13 in pSS patients were increased, and it was closely related to disease activity and lip gland pathological grading, which can be used as an effective indicator for the diagnosis of pSS. Key Points • The TGF-ß1 and CXCL13 levels in the pSS group were higher than those in the control group. • The TGF-ß1 and CXCL13 levels in pSS patients were positively correlated with disease activity and lip gland pathological grading. • TGF-ß1 and CXCL13 can be used as an effective indicator for the diagnosis of pSS.

A patient with pseudohypoparathyroidism type 1A previously misdiagnosed as hereditary multiple exostosis: A case report.

Pseudohypoparathyroidism type 1A (PHP1A), a rare hereditary disorder, is featured by end-organ resistance to parathyroid hormone and Albright's hereditary osteodystrophy. Heterozygous mutation of guanine nucleotide-binding protein α stimulating (GNAS) gene causes the half decreased bioactivity of the Gsα protein levels. Due to the diverse early clinical manifestations of PHP1A, a diagnosis of PHP1A is often easily overlooked and misdiagnosis or missed diagnosis is common. The present study described a girl who was initially diagnosed with hereditary multiple exostoses, but was afterwards confirmed with PHP1A. Moreover, genetic analysis indicated a new mutation (c2277deIC) of the gene.

A facile fluorescence platform for chromium and ascorbic acid detection based on "on-off-on" strategy.

In this paper, a facile and rapid fluorescence "on-off-on" strategy for the detection of chromium (Cr(VI)) and ascorbic acid (AA) was developed, which was based on the water-soluble carbon dots (CDs). The CDs was synthesized by a microwave-assisted treatment of L-tartaric acid, citric acid, and urea. The CDs have many advantages, such as high fluorescence quantum yield (20.5%) and good fluorescence stability. Based on inner filter effect (IFE) and static quenching, the fluorescence of the CDs can be quenched by Cr(VI) quickly; while the reduction of IFE and reducing action can make the fluorescence of the CDs recover by AA efficiently. Moreover, under the optimal experimental conditions, the CDs had a good detection performance for Cr(VI) in the range of 0.8 âˆ¼ 189 µM with the limit of detection (LOD) of 0.16 µM. The linear detection for AA was ranged from 0.43 to 25.7 µM with a LOD of 0.1 µM. More importantly, the as-constructed fluorescence detecting platform was successfully applied for Cr(VI) and AA detection in the environmental samples and fruit samples, respectively. In addition, the application potential of the CDs in fluorescent films and anti-counterfeiting materials was further discussed in detail. This work will provide a novel idea for designing a portable sensor based on the CDs to quickly and sensitively detect Cr(VI) and AA.

Association of Mycoplasma pneumoniae coinfection with adenovirus pneumonia severity in children.

Between the winter of 2018 and the end of 2019, there has been an epidemic of adenovirus infection in southern China, including Zhejiang Province. The number of children suffering from adenovirus pneumonia (AP) has significantly increased. AP can be accompanied by Mycoplasma pneumoniae in children. This study aimed to investigate the association of M. pneumoniae and identify the risk factors for coinfection on hospitalized patients with AP. The patients were classified into two groups by etiologic analysis (single AP and AP with M. pneumoniae coinfection groups). The clinical manifestations, clinical medication, and laboratory and imaging findings of the two groups were compared and analyzed. The coinfection group (n = 125) had a significantly longer duration of fever than the single AP group (n = 171; P = 0.03). Shortness of breath (P = 0.023) and pulmonary imaging findings, such as pulmonary consolidation, atelectasis, pleural effusion, and multilobe lesions (P < 0.05), were more common in the coinfection group. The patients with coinfection had more severe symptoms, significantly longer hospitalization time and an increased proportion of using glucocorticoids and/or immunoglobulin needing oxygen inhalation (P < 0.05). The incidence of AP with M. pneumoniae coinfection is high. The prolonged fever duration and pulmonary imaging findings could be used as prediction factors to predict M. pneumoniae coinfection in children with AP. Patients with AP coinfected with MP may easily develop severe illness. Hence, a reasonable change in the treatment is necessary.

Protective Effect of Zengye Decoction () on Submandibular Glands in Nonobese Diabetic Mice.

OBJECTIVE: To investigate the protective effect of Zengye Decoction (, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice. METHODS: Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction. RESULTS: Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05). CONCLUSIONS: ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.

[Probing into Second Pathological Factors of Sjögren's Syndrome].

Sjögren's syndrome is a chronic autoimmune disease with unclear etiology. From the point of etiology, Chinese medicine (CM) theory holds that pathological products like dry toxin, blood stasis are produced in the pathological process. They are both pathologic results and pathogenic factors for its further development. So pathological products are also named as second pathogenic factors. In this article, the concept of second pathogenic factors was sorted and defined. Main second pathogenic factors of Sjögren's syndrome were pinpointed, and their modern medical bases were analyzed. Authors came to a conclusion that clearing away second pathogenic factors is a key point in treating Sjögren's syndrome.

Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection.

The present study aimed to investigate the protective effects of iptakalim, an adenosine triphosphate (ATP)-sensitive potassium channel opener, on the inflammation of the pulmonary artery and endothelial cell injury in a hypoxia-induced pulmonary arterial hypertension (PAH) rat model. Ninety-six Sprague-Dawley rats were placed into normobaric hypoxia chambers for four weeks and were treated with iptakalim (1.5 mg/kg/day) or saline for 28 days. The right ventricle systolic pressures (RVSP) were measured and small pulmonary arterial morphological alterations were analyzed with hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the content of interleukin (IL)-1ß and IL-10. Immunohistochemical analysis for ED1(+) monocytes was performed to detect the inflammatory cells surrounding the pulmonary arterioles. Western blot analysis was performed to analyze the expression levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and endothelial nitric oxide synthase (eNOS) in the lung tissue. Alterations in small pulmonary arteriole morphology and the ultrastructure of pulmonary arterial endothelial cells were observed via light and transmission electron microscopy, respectively. Iptakalim significantly attenuated the increase in mean pulmonary artery pressure, RVSP, right ventricle to left ventricle plus septum ratio and small pulmonary artery wall remodeling in hypoxia-induced PAH rats. Iptakalim also prevented an increase in IL-1ß and a decrease in IL-10 in the peripheral blood and lung tissue, and alleviated inflammatory cell infiltration in hypoxia-induced PAH rats. Furthermore, iptakalim enhanced PECAM-1 and eNOS expression and prevented the endothelial cell injury induced by hypoxic stimuli. Iptakalim suppressed the pulmonary arteriole and systemic inflammatory responses and protected against the endothelial damage associated with the upregulation of PECAM-1 and eNOS, suggesting that iptakalim may represent a potential therapeutic agent for PAH.

Ruscogenin attenuates monocrotaline-induced pulmonary hypertension in rats.

Inflammation, endothelial dysfunction, and thrombosis contribute to the pathogenesis and development of human pulmonary arterial hypertension (PAH). The aim of this study was to investigate the effects of ruscogenin, a natural anti-inflammatory and anti-thrombotic agent, on the development of monocrotaline (MCT)-induced PAH in rats. Our results revealed that ruscogenin had favorable effects on hemodynamics and pulmonary vascular remodeling, preventing the development of PAH 3 weeks after MCT. In addition, ruscogenin resulted in markedly reduced expression of inflammatory cytokine and leukocyte infiltration via the inhibition of nuclear factor (NF)-κB activity in rat lungs. Ruscogenin also attenuated MCT-induced endothelial cell apoptosis in the remodeled pulmonary arterioles and rescued destruction of endothelial cell membrane proteins such as eNOS, caveolin-1, and CD31. Our findings suggest that ruscogenin might have therapeutic benefits for PAH patients.