UNASSIGNED: The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal.
UNASSIGNED: To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS.
UNASSIGNED: This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks\' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023.
UNASSIGNED: Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure.
UNASSIGNED: The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks\' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models.
UNASSIGNED: Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55).
UNASSIGNED: In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.

BACKGROUND: Particulate β-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown.
METHODS: C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF).
RESULTS: The 150 mg/kg OAW treatment mitigated OVA-induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)-α and IL-6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF.
CONCLUSIONS: These results highlight OAW\'s robust anti-inflammatory properties, suggesting potential benefits in treating MC-dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.

Monitoring airway impedance has significant clinical value in accurately assessing and diagnosing pulmonary function diseases at an early stage. To address the issue of large oscillator size and high power consumption in current pulmonary function devices, this study adopts a new strategy of expiration-driven oscillation. A lightweight and low-power airway impedance monitoring system with integrated sensing, control circuitry, and dynamic feedback system, providing visual feedback on the system\'s status, was developed. The respiratory impedance measurement experiments and statistical comparisons indicated that the system could achieve stable measurement of airway impedance at 5 Hz. The frequency spectrum curves of respiratory impedance ( R and X) showed consistent trends with those obtained from the clinical pulmonary function instrument, specifically the impulse oscillometry system (IOS). The differences between them were all less than 1.1 cm H 2O·s/L. Additionally, there was a significant statistical difference in the respiratory impedance R5 between the exercise and rest groups, which suggests that the system can measure the variability of airway resistance parameters during exercise. Therefore, the impedance monitoring system developed in this study supports subjects in performing handheld, continuous measurements of dynamic changes in airway impedance over an extended period of time. This research provides a foundation for further developing low-power, portable, and even wearable devices for dynamic monitoring of pulmonary function.
气道阻抗的监测对肺功能疾病的准确评估及早期诊断具有重要临床价值。针对当前肺功能设备中振荡源系统体积大、功耗高等难以满足动态测量需求的问题，本研究采用可控呼气振荡与状态可视化反馈的新策略，设计了微型电磁振荡源、集成传感控制电路和动态反馈系统，开发了一种结构轻巧、功耗低及带可视化状态反馈的气道阻抗监测系统。呼吸阻抗测量实验及统计对比结果表明，该系统可实现稳定的5 Hz气道阻抗测量，呼吸系统阻抗（ R和 X）频谱曲线与临床肺功能仪IOS的频谱曲线均具有较为一致的变化趋势，其差值均小于1.1 cm H 2O·s/L；运动与静息状态组的呼吸阻抗 R5差异有统计学意义，且呼吸电抗 X5的波动幅值较大，表明本系统能测量气道阻力参数的动态变异性。因此，本研究开发的阻抗监测系统支持受试者可手持移动、较长时间段内连续测量气道阻抗的动态变化，为进一步开发低功耗、便携化甚至可穿戴的动态肺功能监测设备提供了研究基础。.

The prevalence of allergic diseases has dramatically increased among children in recent decades. These conditions significantly impact the quality of life of allergic children and their families. Lactoferrin, a multifunctional glycoprotein found in various biological fluids, is emerging as a promising immunomodulatory agent that can potentially alleviate allergic diseases in children. Lactoferrin\'s multifaceted properties make it a compelling candidate for managing these conditions. Firstly, lactoferrin exhibits potent anti-inflammatory and antioxidant activities, which can mitigate the chronic inflammation characteristic of allergic diseases. Secondly, its iron-binding capabilities may help regulate the iron balance in allergic children, potentially influencing the severity of their symptoms. Lactoferrin also demonstrates antimicrobial properties, making it beneficial in preventing secondary infections often associated with respiratory allergies. Furthermore, its ability to modulate the immune response and regulate inflammatory pathways suggests its potential as an immune-balancing agent. This review of the current literature emphasises the need for further research to elucidate the precise roles of lactoferrin in allergic diseases. Harnessing the immunomodulatory potential of lactoferrin could provide a novel add-on approach to managing allergic diseases in children, offering hope for improved outcomes and an enhanced quality of life for paediatric patients and their families. As lactoferrin continues to capture the attention of researchers, its properties and diverse applications make it an intriguing subject of study with a rich history and a promising future.

The urokinase-type plasminogen activator receptor (uPAR) is a unique protease binding receptor, now recognized as a key regulator of inflammation. Initially, uPA/uPAR was considered thrombolytic (clot-dissolving); however, recent studies have demonstrated its predominant immunomodulatory functions in inflammation and cancer. The uPA/uPAR complex has a multifaceted central role in both normal physiological and also pathological responses. uPAR is expressed as a glycophosphatidylinositol (GPI)-linked receptor interacting with vitronectin, integrins, G protein-coupled receptors, and growth factor receptors within a large lipid raft. Through protein-to-protein interactions, cell surface uPAR modulates intracellular signaling, altering cellular adhesion and migration. The uPA/uPAR also modifies extracellular activity, activating plasminogen to form plasmin, which breaks down fibrin, dissolving clots and activating matrix metalloproteinases that lyse connective tissue, allowing immune and cancer cell invasion and releasing growth factors. uPAR is now recognized as a biomarker for inflammatory diseases and cancer; uPAR and soluble uPAR fragments (suPAR) are increased in viral sepsis (COVID-19), inflammatory bowel disease, and metastasis. Here, we provide a comprehensive overview of the structure, function, and current studies examining uPAR and suPAR as diagnostic markers and therapeutic targets. Understanding uPAR is central to developing diagnostic markers and the ongoing development of antibody, small-molecule, nanogel, and virus-derived immune-modulating treatments that target uPAR.

OBJECTIVE: To explore the effects of iris xanthin on airway inflammation, airway remodeling, and the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in asthmatic young mice.
METHODS: Sixty male BALB/c young mice were randomly assigned into six groups: a blank group, a model group, a dexamethasone group, and low, medium, and high dose groups of iris xanthin, with ten mice per group. Asthma models were induced through intraperitoneal injections of a sensitizing agent [ovalbumin (OVA) 20 μg + aluminum hydroxide gel 2 mg], followed by 4% OVA aerosol inhalation. Lung function was measured using a pulmonary function tester to determine lung volume (LV), resting ventilation per minute (VE), and airway reactivity (Penh value). Hematoxylin-eosin (HE) staining was employed to examine and analyze airway remodeling. The contents of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid were quantified using ELISA. Real-time fluorescence quantitative polymerase chain reaction and Western blot analysis were used to assess the expression of HMGB1/TLR4/NF-κB pathway-related mRNA and proteins in lung tissues.
RESULTS: Compared to the model group, the dexamethasone and iris xanthin-treated groups (low, medium, and high doses) exhibited significant increases in LV and VE (P<0.05), with incremental dose-dependent increases observed in the iris xanthin groups. Additionally, Penh values, IL-1β, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, and NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were all reduced (P<0.05) in a dose-dependent manner. When compared to the dexamethasone group, the low and medium dose iris xanthin groups showed decreases in LV and VE (P<0.05), whereas Penh values, IL-1β, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were increased (P<0.05). No significant differences were noted in these indices between the high dose iris xanthin group and the dexamethasone group (P>0.05).
CONCLUSIONS: Iris xanthin can effectively alleviates airway inflammation and inhibits airway remodeling in asthmatic young mice, possibly through the suppression of the HMGB1/TLR4/NF-κB pathway.
目的: 探究鸢尾黄素对哮喘幼鼠气道炎症、气道重塑及高迁移率族蛋白B1（high mobility group box 1 protein, HMGB1）/Toll样受体4（Toll-like receptor 4, TLR4）/核因子κB（nuclear factor-κB, NF-κB）通路的影响。方法: 将60只雄性BALB/c幼鼠随机分为空白组、模型组、地塞米松组，以及鸢尾黄素低、中、高剂量组，每组10只。采用腹腔注射致敏剂［卵清蛋白（ovalbumin, OVA）20 μg+氢氧化铝凝胶2 mg］+4% OVA雾化吸入激发建立幼鼠哮喘模型。肺功能检测仪检测幼鼠肺容积（lung volume, LV）、每分钟静息通气量（resting ventilation per minute, VE）及气道反应性（Penh值）；苏木精-伊红染色观察并分析气道重塑情况；ELISA法检测肺泡灌洗液中白介素（interleukin, IL）-1β、IL-6、肿瘤坏死因子α（tumor necrosis factor alpha, TNF-α）含量；实时定量逆转录聚合酶链反应及Western blot法检测肺组织中HMGB1/TLR4/NF-κB通路相关mRNA及蛋白表达。结果: 与模型组比较，地塞米松组及鸢尾黄素低、中、高剂量组LV、VE均显著升高（P<0.05），其中鸢尾黄素各剂量组随剂量增加LV、VE升高（P<0.05）；地塞米松组及鸢尾黄素低、中、高剂量组Penh值、IL-1β、IL-6、TNF-α、气道重塑指标，以及HMGB1、TLR4、NF-κB p65 mRNA和HMGB1、TLR4、p-NF-κB p65蛋白表达水平均降低（P<0.05），其中鸢尾黄素各剂量组随剂量增加上述指标降低（P<0.05）。与地塞米松组比较，鸢尾黄素低、中剂量组LV、VE均降低（P<0.05），Penh值、IL-1β、IL-6、TNF-α、气道重塑指标，以及HMGB1、TLR4、NF-κB p65 mRNA和HMGB1、TLR4、p-NF-κB p65蛋白表达水平均升高（P<0.05）；鸢尾黄素高剂量组上述指标与地塞米松组比较差异无统计学意义（P>0.05）。结论: 鸢尾黄素能有效减轻哮喘幼鼠气道炎症，抑制气道重塑，可能与抑制HMGB1/TLR4/NF-κB通路有关。.

OBJECTIVE: To investigate the structural characteristics of intestinal flora in children with sepsis and its association with inflammatory response.
METHODS: A prospective cohort study was conducted. The children with sepsis who were admitted from December 2021 to January 2023 were enrolled as the sepsis group, and the children with non-sepsis who were admitted during the same period were enrolled as the non-sepsis group. The two groups were compared in terms of the distribution characteristics of intestinal flora, peripheral white blood cell count (WBC), C reactive protein (CRP), and cytokines, and the correlation of the relative abundance of fecal flora with WBC, CRP, and cytokines was analyzed.
RESULTS: At the genus level, compared with the non-sepsis group, the sepsis group had significantly lower relative abundance of Akkermansia, Ruminococcus, and Alistipes and significantly higher relative abundance of Enterococcus, Streptococcus, and Staphylococcus (P<0.05). At the phylum level, Proteobacteria was the dominant phylum (37.46%) in the group of children with a score of ≤70 from the Pediatric Critical Illness Score (PICS), and Firmicutes was the dominant phylum in the group of children with a score of 71-80 or 81-90 from the PICS (72.20% and 43.88%, respectively). At the genus level, among the 18 specimens, 5 had a relative abundance of >50% for a single flora. Compared with the non-sepsis group, the sepsis group had significant higher levels of WBC, CRP, interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (P<0.05). The Spearman\'s rank correlation analysis showed that at the genus level, the relative abundance of Ruminococcus, Alistipes, and Parasutterella in the sepsis group was negatively correlated with the levels of WBC, CRP, and IL-6 (P<0.05); the relative abundance of Enterococcus was positively correlated with the CRP level (P<0.01); the relative abundance of Streptococcus and Staphylococcus was positively correlated with the levels of CRP and IL-6 (P<0.05); the relative abundance of Streptococcus was positively correlated with WBC (P<0.05).
CONCLUSIONS: Intestinal flora disturbance is observed in children with sepsis, and its characteristics vary with the severity of the disease. The structural changes of intestinal flora are correlated with inflammatory response in children with sepsis.
目的: 探讨脓毒症患儿肠道菌群结构特征及其与炎症反应的相关性。方法: 采用前瞻性队列研究方法，纳入2021年12月—2023年1月收治的脓毒症患儿为研究对象（设为脓毒症组），选择同期住院的感染非脓毒症患儿为对照（设为非脓毒症组）。比较两组患儿肠道菌群分布特征、外周白细胞（white blood cell, WBC）计数、C-反应蛋白（C-reactive protein, CRP）、细胞因子水平的差异，并将大便菌群相对丰度与WBC计数、CRP、细胞因子水平进行相关性分析。结果: 属水平上，脓毒症组阿克曼氏菌属、瘤胃球菌属及另枝杆菌属相对丰度低于非脓毒症组，肠球菌属、链球菌属、葡萄球菌属相对丰度高于非脓毒症组（P<0.05）。门水平上，脓毒症患儿小儿危重症评分≤70分组以变形菌门为优势菌门（37.46%），71~80分组和81~90分组优势菌门为厚壁菌门（分别为72.20%、43.88%）。属水平上，18例标本中5例标本单一菌群相对丰度超过50%。脓毒症组WBC计数、CRP、白介素（interleukin, IL）-6、IL-10、肿瘤坏死因子-α水平高于非脓毒症组（P<0.05）。Spearman秩相关性分析显示：在属水平上，脓毒症组瘤胃球属、另枝杆菌属、副萨特氏菌属相对丰度与WBC计数、CRP、IL-6水平均呈负相关（P<0.05）；肠球菌属相对丰度与CRP水平呈正相关（P<0.01）；链球菌属、葡萄球菌属等相对丰度与CRP、IL-6水平均呈正相关（P<0.05）；链球菌属相对丰度与WBC计数呈正相关（P<0.05）。结论: 脓毒症患儿肠道菌群呈紊乱状态，且随病情程度不同具有特征性；脓毒症患儿肠道菌群结构改变与机体炎症反应具有相关性。.

UNASSIGNED: Dentin hypersensitivity (DH) is a prevalent condition, but long-term effective treatments are scarce. Differentiation of odontoblast-like cells is promising for inducing tertiary dentinogenesis and ensuring sustained therapeutic efficacy against DH. This study examined the effects and mechanism of action of mild heat stress (MHS) on the differentiation of odontoblast-like MDPC-23 cells.
UNASSIGNED: We used a heating device to accurately control the temperature and duration, mimicking the thermal microenvironment of odontoblast-like cells. Using this device, the effects of MHS on cell viability and differentiation were examined. Cell viability was assessed using the MTT assay. The expression and nucleoplasmic ratio of the yes-associated protein (YAP) were examined by western blotting and immunofluorescence. The gene expression levels of heat shock proteins (HSPs) and dentin matrix protein-1 (DMP1) were measured using qPCR. Dentin sialophosphoprotein (DSPP) expression was evaluated using immunofluorescence and immunoblotting. Verteporfin was used to inhibit YAP activity.
UNASSIGNED: Mild heat stress (MHS) enhanced the odontoblast differentiation of MDPC-23 cells while maintaining cell viability. MHS also increased YAP activity, as well as the levels of HSP25 mRNA, HSP70 mRNA, HSP90α mRNA, DMP1 mRNA, and DSPP protein. However, after YAP inhibition, both cell viability and the levels of HSP90α mRNA, DMP1 mRNA, and DSPP protein were reduced.
UNASSIGNED: YAP plays a crucial role in maintaining cell viability and promoting odontoblast differentiation of MDPC-23 cells under MHS. Consequently, MHS is a potential therapeutic strategy for DH, and boosting YAP activity could be beneficial for maintaining cell viability and promoting odontoblast differentiation.

BACKGROUND: Coronary perfusion pressure (CPP) indicates spontaneous return of circulation and is recommended for high-quality cardiopulmonary resuscitation (CPR). This study aimed to investigate a method for non-invasive estimation of CPP using electrocardiography (ECG) and photoplethysmography (PPG) during CPR.
METHODS: Nine pigs were used in this study. ECG, PPG, invasive arterial blood pressure (ABP), and right atrial pressure (RAP) signals were simultaneously recorded. The CPPs were estimated using three datasets: (a) ECG, (b) PPG, and (c) ECG and PPG, and were compared with invasively measured CPPs. Four machine-learning algorithms, namely support vector regression, random forest (RF), K-nearest neighbor, and gradient-boosted regression tree, were used for estimation of CPP.
RESULTS: The RF model with a combined ECG and PPG dataset achieved better estimation of CPP than the other algorithms. Specifically, the mean absolute error was 4.49 mmHg, the root mean square error was 6.15 mm Hg, and the adjusted R2 was 0.75. A strong correlation was found between the non-invasive estimation and invasive measurement of CPP (r = 0.88), which supported our hypothesis that machine-learning-based analysis of ECG and PPG parameters can provide a non-invasive estimation of CPP for CPR.
CONCLUSIONS: This study proposes a novel estimation of CPP using ECG and PPG with machine-learning-based algorithms. Non-invasively estimated CPP showed a high correlation with invasively measured CPP and may serve as an easy-to-use physiological indicator for high-quality CPR treatment.

Although multiple purinergic receptors mediate the analgesic effects of acupuncture, it remains unclear whether there is mutual interaction between purinergic receptors to jointly mediate the electroacupuncture inhibition of peripheral sensitization in visceral pain. Visceral hypersensitivity was induced by intracolonic 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rat. The antinociception effect of electroacupuncture on visceral pain was evaluated by morphology, behaviors, neuroelectrophysiology and molecular biology techniques. After labeling the colon-related primary sensory neurons with neural retrograde tracer and employing neuropharmacology, neuroelectrophysiology, and molecular biotechnology, the mechanisms of P2X7R, P2Y1R, and P2X3R in colon-related dorsal root ganglion (DRG) neurons alleviating visceral hypersensitivity of irritable bowel syndrome (IBS) by electroacupuncture at Zusanli and Sanyinjiao acupoints.were elucidated from the perspective of peripheral sensitization. Electroacupuncture significantly inhibited TNBS-induced colonic hypersensitivity in rats with IBS, and Satellite Glial Cells (SGCs) in DRG were found to be involved in electroacupuncture-mediated regulation of the electrophysiological properties of neurons. P2X7R was found to play a pain-inducing role in IBS visceral hypersensitivity by affecting P2X3R, and electroacupuncture exerted an analgesic effect by inhibiting P2X7R activation. P2Y1R was found to play an analgesic role in the process of visceral pain, mediating electroacupuncture to relieve visceral hypersensitivity. P2Y1R relieved visceral pain by inhibiting P2X3R in neurons associated with nociception, with P2X7R identified as upstream of P2Y1R up-regulation by electroacupuncture. Our study suggests that the P2X7R → P2Y1R → P2X3R inhibitory pathway in DRG mediates the inhibition of peripheral sensitization by electroacupuncture in rats with IBS visceral hypersensitivity.