BACKGROUND:Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and long-term neurodevelopmental impairment. Secondary neuroinflammation and inflammasome-mediated pyroptosis substantially contribute to progressive brain injury. Procyanidin B2 (PCB2), a plant-derived proanthocyanidin abundant in several traditional botanicals, exhibits anti-inflammatory activity, but its role in neonatal hypoxic-ischemic brain injury remains unclear. OBJECTIVE:To determine whether PCB2 protects against neonatal hypoxic-ischemic brain damage (HIBD) in rat and to clarify whether the TLR4/NF-κB pathway-driven pyroptosis is involved. METHODS:A Rice-Vannucci hypoxic-ischemic brain injury model was established in postnatal day 7 Sprague-Dawley rats. Brain injury was assessed by H&E, Nissl staining, ultrastructural analysis, and long-term behavioral tests at P28. Transcriptomic profiling and enrichment analyses were used to identify key pathways. qRT-PCR, Western blotting, and immunofluorescence were performed to evaluate TLR4/MyD88/NF-κB signaling and pyroptosis markers. TLR4 gain- and loss-of-function experiments were conducted in OGD-injured BV2 microglial cells. Molecular docking was applied to predict the potential PCB2-TLR4 interaction. RESULTS:PCB2 markedly reduced histopathological damage and improved P28 cognitive performance, accompanied by restoration of synaptic/neuronal markers. Transcriptomics identified enrichment of Toll-like receptor and cytokine-related inflammatory pathways among PCB2-reversed genes. PCB2 suppressed TLR4/MyD88/NF-κB activation and decreased NLRP3 inflammasome/pyroptosis proteins (NLRP3, ASC, caspase-1, GSDMD-N) and IL-1β/IL-18 (all P < 0.05). TLR4 overexpression attenuated, whereas TLR4 silencing enhanced, PCB2's anti-pyroptotic effects in vitro. Molecular docking predicted a potential interaction between PCB2 and TLR4. CONCLUSIONS:PCB2 alleviates neonatal hypoxic-ischemic brain injury by inhibiting TLR4/NF-κB-dependent pyroptosis, supporting its potential as a therapeutic candidate for neonatal HIBD.

CONTEXT:Vitamin D (VD) is integral to lung maturation and immune regulation, yet its association with neonatal respiratory diseases remains debated. OBJECTIVES:This study aimed to clarify the association between vitamin D (VD) status and neonatal respiratory diseases, to quantify the risk posed by VD deficiency (VDD), and to evaluate the therapeutic benefits of VD supplementation. DATA SOURCES:A comprehensive search was conducted in PubMed, Web of Science, EMBASE, and other major databases for studies published up to October 1, 2025. DATA EXTRACTION:Following the PRISMA guidelines, 2 reviewers independently screened the studies, extracted data, and assessed its quality. Observational studies and randomized controlled trials (RCTs) were included. DATA ANALYSIS:Thirty-one studies (23 observational, 8 RCTs) involving over 3000 neonates were analyzed using a random-effects meta-analysis. Neonates with respiratory disease exhibited significantly lower 25(OH)D levels (standardized mean difference, SMD = -0.66; 95% CI: -0.90 to -0.41). Vitamin D deficiency was associated with an increased risk of respiratory distress syndrome (RDS) (adjusted odds ratio [aOR] = 2.57; 95% CI: 1.55-4.24); however, this association was attenuated after adjusting for publication bias. Vitamin D supplementation effectively restored VD status (SMD = 2.80, 95% CI: 1.70-3.89) and may reduce morbidity, particularly with higher doses (800-1000 IU/day) or maternal administration. CONCLUSIONS:Vitamin D deficiency represents a significant risk marker, but its role as an independent causal factor may be overestimated. Supplementation, particularly with higher doses or maternal administration, is a feasible adjunct strategy, but high-quality RCTs are imperative for establishing definitive intervention protocols. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration No. CRD420251152942.

BACKGROUND:Neonatal sepsis is a leading cause of morbidity and mortality, often complicated by acute lung injury (ALI). Current treatments lack targeted anti-inflammatory or antioxidant strategies. Sulodexide (SDX), a glycosaminoglycan with endothelial-protective, anti-inflammatory, and antioxidant properties, may offer therapeutic benefit. METHODS:A lipopolysaccharide (LPS)-induced neonatal rat model was used to evaluate the effects of SDX. Following LPS injection, neonatal rats received SDX at different doses. Survival, lung histopathology, wet-to-dry lung weight ratios, and serum procalcitonin levels were assessed. Endothelial glycocalyx integrity was examined by transmission electron microscopy. Cytokines and oxidative stress markers were measured by western blotting and antioxidant assays. Transcriptomic changes were analyzed by RNA sequencing and validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS:SDX improved survival, reduced pulmonary edema, and alleviated histopathological lung damage. Endothelial glycocalyx structure was partially preserved. SDX reduced levels of interleukin-1β (IL-1β), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α), and increased total antioxidant capacity. Transcriptome analysis identified the TNF signaling pathway as a key target, with downregulation of suppressor of cytokine signaling 3 (SOCS3), phosphorylated c-Jun N-terminal kinase (p-JNK), and nuclear factor kappa B (NF-κB), and upregulation of mitogen-activated protein kinase phosphatase 1 (MKP1). CONCLUSION:SDX attenuates LPS-induced ALI in neonatal rats by modulating inflammation, particularly through the TNF-α signaling pathway. These findings suggest the potential of SDX as a therapeutic agent for neonatal sepsis-associated ALI. IMPACT:Sulodexide, a drug that has been used clinically for nearly four decades primarily in the management of adult vascular disorders, demonstrates both safety and therapeutic efficacy in a neonatal rat model of sepsis. This study provides the first experimental evidence supporting the repurposing of sulodexide for neonatal sepsis-associated acute lung injury. Sulodexide significantly attenuates inflammatory lung injury by modulating TNF-α pathway. These findings highlight sulodexide as a promising and readily translatable anti-inflammatory therapy for neonatal sepsis.

Neonatal hypoxic-ischemic brain damage is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy, whose clinical treatment is still limited to therapeutic hypothermia with limited efficacy. N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC), a derivative of N-acetylserotonin, has shown neuroprotective properties. This study was conducted to evaluate the neuroprotective and molecular mechanisms of HIOC. We established an in vitro model using Oxygen-glucose deprivation/reoxygenation (OGD/R) in HT22 cells, alongside an in vivo model via the modified Rice-Vannucci method. The results showed that HIOC reduced OGD/R-induced HT22 cell pyroptosis and inhibited NOD-like receptor pyrin domain- containing protein 3 (NLRP3) inflammasome activation. With the addition of the mitophagy inhibitor 3-MA, we demonstrated that HIOC promoted PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy to reduce HT22 cell pyroptosis. Mechanistically, HIOC stimulated mitophagy to remove damaged mitochondria. The clearance of injured mitochondria reduced reactive oxygen species generation, which consequently inhibited NLRP3 inflammasome expression. In vivo, HIOC remarkably lessened cerebral blood flow, infarct volume, neuronal injury by activating mitophagy. HIOC activated mitophagy to produce antipyroptosis effects. Together, our finding demonstrated that HIOC improves brain injury by promoting PINK1/Parkin-dependent mitophagy to inhibit NLRP3 inflammasome activation and pyroptosis, suggesting its potential for hypoxic-ischemic brain damage treatment.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the IL‑1 protein data shown in the western blotting data in Fig. 5A on p. 1905, the hippocampal images shown in Fig. 6A and certain of the immunohistochemical data shown in Fig. 6B on p. 1906 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time. In view of the fact that certain of the abovementioned data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 1899‑1908, 2018; DOI: 10.3892/mmr.2018.9227].

MicroRNA-124 (miR-124) is implicated in various neurological diseases; however, its significance in hypoxic-ischaemic brain damage (HIBD) remains unclear. This study aimed to elucidate the underlying pathophysiological mechanisms of miR-124 in HIBD. In our study performed on oxygen-glucose deprivation followed by reperfusion (OGD)/R-induced primary cortical neurons, a substantial reduction in miR-124 was observed. Furthermore, the upregulation of miR-124 significantly mitigated oxidative stress, apoptosis, and mitochondrial impairment. We demonstrated that miR-124 interacts with the signal transducer and activator of transcription 3 (STAT3) to exert its biological function using the dual-luciferase reporter gene assay. As the duration of OGD increased, miR-124 exhibited a negative correlation with STAT3. STAT3 overexpression notably attenuated the protective effects of miR-124 mimics, while knockdown of STAT3 reversed the adverse effects of the miR-124 inhibitor. Subsequently, we conducted an HIBD model in rats. In vivo experiments, miR-124 overexpression attenuated cerebral infarction volume, cerebral edema, apoptosis, oxidative stress, and improved neurological function recovery in HIBD rats. In summary, the neuroprotective effects of the miR-124/STAT3 axis were confirmed in the HIBD model. MiR-124 may serve as a potential biomarker with significant therapeutic implications for HIBD.

OBJECTIVE:Periventricular-intraventricular hemorrhage is the most common type of intracranial bleeding in newborns, especially in the first 3 days after birth. Severe periventricular-intraventricular hemorrhage is considered a progression from mild periventricular-intraventricular hemorrhage and is often closely associated with severe neurological sequelae. However, no specific indicators are available to predict the progression from mild to severe periventricular-intraventricular in early admission. This study aims to establish an early diagnostic prediction model for severe PIVH.METHOD:This study was a retrospective cohort study with data collected from the MIMIC-III (v1.4) database. Laboratory and clinical data collected within the first 24 h of NICU admission have been used as variables for both univariate and multivariate logistic regression analyses to construct a nomogram-based early prediction model for severe periventricular-intraventricular hemorrhage and subsequently validated.RESULTS:A predictive model was established and represented by a nomogram, it comprised three variables: output, lowest platelet count and use of vasoactive drugs within 24 h of NICU admission. The model's predictive performance showed by the calculated area under the curve was 0.792, indicating good discriminatory power. The calibration plot demonstrated good calibration between observed and predicted outcomes, and the Hosmer-Lemeshow test showed high consistency (p = 0.990). Internal validation showed the calculated area under a curve of 0.788.CONCLUSIONS:This severe PIVH predictive model, established by three easily obtainable indicators within the NICU, demonstrated good predictive ability. It offered a more user-friendly and convenient option for neonatologists.

Background This study aims to identify a novel gene signature for coronary artery disease (CAD), explore the role of immune cell infiltration in CAD pathogenesis, and assess the cell function of mast cell-expressed membrane protein 1 (MCEMP1) in human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL). Methods To identify differentially expressed genes (DEGs) of CAD, datasets GSE24519 and GSE61145 were downloaded from the Gene Expression Omnibus (GEO) database using the R “limma” package with p < 0.05 and |log2 FC| > 1. Gene ontology (GO) and pathway analyses were conducted to determine the biological functions of DEGs. Hub genes were identified using support vector machine-recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO). The expression levels of these hub genes in CAD were validated using the GSE113079 dataset. CIBERSORT program was used to quantify the proportion of immune cell infiltration. Western blot assay and qRT‐PCR were used to detect the expression of hub genes in ox-LDL-treated HUVECs to validate the bioinformatics results. Knockdown interference sequences for MCEMP1 were synthesized, and cell proliferation and apoptosis were examined using a CCK8 kit and Muse® Cell Analyzer, respectively. The concentrations of IL-1β, IL-6, and TNF-α were measured with respective enzyme-linked immunosorbent assay (ELISA) kits. Results A total of 73 DEGs (four down-regulated genes and 69 up-regulated genes) were identified in the metadata (GSE24519 and GSE61145) cohort. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results indicated that these DEGs might be associated with the regulation of platelet aggregation, defense response or response to bacterium, NF-kappa B signaling pathway, and lipid and atherosclerosis. Using SVM-RFE and LASSO, seven hub genes were obtained from the metadata. The upregulated expression of DIRC2 and MCEMP1 in CAD was confirmed in the GSE113079 dataset and in ox-LDL-treated HUVECs. The associations between the two hub genes (DIRC2 and MCEMP1) and the 22 types of immune cell infiltrates in CAD were found. MCEMP1 knockdown accelerated cell proliferation and suppressed cell apoptosis for ox-LDL-treated HUVECs. Additionally, MCEMP1 knockdown appeared to decrease the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Conclusions The results of this study indicate that MCEMP1 may play an important role in CAD pathophysiology.

Hypoxic-ischemic brain damage (HIBD) is one of the major causes of infant death and long-term neurological disturbances, which puts great pressure on families and society. Previous studies have reported that neuroinflammation regulates the pathogenesis of HIBD. MiR-155 has been reported to participate in many brain injuries; however, its direct implication and related mechanisms are not illuminated in HIBD. Herein, we identified that miR-155 plays a vital role in HIBD both in in vitro and in vivo models. We found that miR-155 promoted inflammation and apoptosis via targeting SIRT1 and negatively regulated its expression levels in oxygen-glucose deprivation/reoxygenation (OGD/R) in an in vitro model. Silencing of SIRT1 reversed the effects of miR-155 inhibitor on apoptosis and the NF-κB pathway in OGD/R-treated PC12 cells and microglia (BV2) cells. Moreover, in a neonatal rat HIBD model, miR-155 enhanced apoptosis and inflammation in the brains of rats with HIBD in vivo. Together, our results demonstrated that miR-155 exerted a negative effect in HIBD by targeting SIRT1, which could contribute to the treatment of neonatal patients with hypoxic-ischemic brain damage.

Hypoxic-ischemic encephalopathy (HIE) is a substantial cause of irreversible nerve injury in newborns. As the endogenous precursor of melatonin, N-acetylserotonin (NAS) can cross the blood-brain barrier and exert neu-roprotective effects. Evidence shows that NAS exerts a neuroprotective role in ischemic brain injury by inhibiting the mitochondrial death pathway. This study investigates whether NAS can play a neuroprotective role in the HIE model and explores its underlying molecular mechanism. In vivo, postnatal day 7 (P7) Sprague-Dawley rats were used to construct the HIE rat model. Significant improvement in short-term neurobehavioral impairment, cerebral infarction volume decrease, and neuronal injury mitigation was observed with NAS treatment after hypoxic-ischemic (HI) injury. In addition, we validated that NAS suppressed NOD-like receptor pyrin domain -containing protein 3 (NLRP3) inflammasome activation and NLRP3 inflammasome-related protein expression in the HIE model. Furthermore, we demonstrate that NAS reduced mitochondrial membrane potential loss, oxidative damage to mitochondrial DNA (mtDNA), cytosolic mtDNA copy number and activation of its down-stream cyclic guanosine monophosphate adenylate synthase (cGAS)/ stimulator of interferon genes (STING) pathway. Additionally, we further verified the activation of NAS on the AMP-activated protein kinase (AMPK)/ peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha)/ mitochondrial transcription factor A (TFAM) pathway and found that inhibition of AMPK could increase cytosolic mtDNA copy number and NLRP3 inflammasome-related protein expression while decreasing STING protein expression. Our study demonstrated that NAS inhibits oxidative mtDNA-induced neuroinflammation, which is partially associated with AMPK/PGC-1 alpha/TFAM pathway activation in the HIE model.

Background: Due to the limitation of blood culture diagnosis, this study sought to evaluate the cerebral hemodynamic changes by Doppler ultrasound for timely and objective diagnosis techniques in preterm infants with early onset-neonatal sepsis. Methods: In this retrospective study, 86 preterm infants treated at the Department of Neonatology, Renmin Hospital of Wuhan University from January 1, 2019 to March 31, 2021, were divided into the following 2 groups: (I) the early onset neonatal sepsis (EONS) group (G1, n=41); (II) the normal control group (G2, n=45). The cerebral hemodynamic changes were examined by transcranial ultrasound. Stata15.0 and SPSS26.0 software were used for the data analysis. The pair-wise comparisons of the receiver operating characteristic (ROC) curves were on the MedCalc18.2.1 software. For all the statistical analyses, P value <0.05 was considered significant. Results: Sex, birth weight, and gestational age did not differ significantly between the groups (P>0.05); the peak systolic velocity (PSV), mean velocity (MV), end diastolic velocity (EDV) (cm/ s), resistivity index (RI), pulsatility index (PI) of the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) differed significantly between 2 groups (P<0.05). In relation to the diagnostic sensitivity, the area under the receiver operating characteristic (AUROC) analyses showed that compared to IL-6 (0.95, 1.00), EDV of the ACA, and PSV, EDV and MV of the MCA and PCA had a higher sensitivity than the others (AUROC: 1, all 95% CI: 1.00, 1.00). The diagnostic points of the EDV and MV of the ACA were 9.8 and 17.3 cm/s, respectively, the PSV, EDV, and MV of the MCA were 55.9, 10.9, and 20.4 cm/s, respectively, and the PSV, EDV, and MV of the PCA were 27.5, 7.5, and 9.8 cm/s, respectively. Conclusions: The study showed that PI increases and RI decreases, MV increases, and cerebral blood flow increases in EONS. Further, the EDV and MV of the ACA and the PSV, EDV, and MV of the MCA and PCA showed higher sensitivity than IL-6.

目的 观察急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)新生儿支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)炎性因子、肺泡表面活性蛋白(surfactant protein,SP)水平变化,探讨其与新生儿发生ARDS的相关性.方法 需机械通气的ARDS新生儿30例为ARDS组,根据氧合指数分为轻度组(氧合指数4.0～＜8.0)11例,中度组(氧合指数8.0～＜16.0)12例,重度组(氧合指数≥16.0)7例;因其他疾病需机械通气新生儿25例为对照组.比较ARDS组与对照组应用肺表面活性物质、脓毒症、窒息比率及机械通气时间等.ARDS组于呼吸机上机前、上机24 h时、撤机前,对照组于呼吸机上机前收集BALF,采用ELISA法检测BALF白细胞介素(interleukin,IL)-6、IL-10、IL-17、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、SP-A、SP-D水平;比较上机前ARDS组与对照组及ARDS组上机前、上机24 h时、撤机前BALF IL-6、IL-10、IL-17、TNF-α、SP-A、SP-D水平,比较轻、中、重度组上机24 h时 BALF IL-6、IL-10、IL-17、TNF-α、SP-A、SP-D水平.采用 Pearson 相关分析 ARDS新生儿上机 24 h 时 BALF SP-A 水平与IL-6、IL-10、IL-17、TNF-α水平的相关性;采用多因素 logistic回归分析新生儿发生ARDS的影响因素.结果 ARDS组应用肺泡表面活性物质、脓毒症、窒息比率(86.67％、40.00％、46.67％)均高于对照组(20.00％、4.00％、8.00％)(x2=6.857,P＜0.001;x2=7.329,P＜0.001;x2=8.968,P＜0.001),机械通气时间[(4.20±1.50)d]长于对照组[(1.00±0.20)d](t=2.432,P=0.004).上机前 ARDS 组 BALF IL-6[(198.32±10.23)ng/L]、IL-17[(118.42±73.55)ng/L]、TNF-α[(52.63±9.77)ng/L]水平均高于对照组[(125.61±10.39)、(98.03±54.91)、(42.67±15.31)ng/L](P＜0.05),SP-A[(38.96±1.24)ng/L]、SP-D[(9.71±0.07)ng/L]水平 均低于 对照组[(45.95±1.87)、(12.62±0.05)ng/L](P＜0.05),IL-10 水平与对照组比较差异无统计学意义(P＞0.05).上机 24 h时ARDS组BALF IL-6、IL-17、TNF-α水平均高于上机前、撤机前(P＜0.05),SP-A、SP-D水平均低于上机前、撤机前(P＜0.05);ARDS组撤机前BALF IL-6、IL-17、TNF-α水平均低于上机前(P＜0.05),SP-A、SP-D水平均高于上机前(P＜0.05);ARDS组上机前、上机24 h时、撤机前BALF IL-10水平比较差异无统计学意义(P＞0.05).轻、中、重度组上机24 h时BALF IL-6、IL-17、TNF-α水平均依次升高(P＜0.05),SP-A、SP-D水平均依次降低(P＜0.05),IL-10水平比较差异无统计学意义(P＞0.05).上机24 h时ARDS新生儿BALF SP-A水平与IL-6、TNF-α水平均呈负相关(r=-0.389,P=0.006;r=-0.465,P=0.005),与 IL-10、IL-17 水平均无线性相关性(r=0.291,P=0.162;r=-0.268,P=0.087).BALF SP-A(OR=0.763,95％CI:0.653～0.978,P=0.035)、SP-D(OR=0.682,95％CI:0.512～0.915,P=0.027)、IL-6(OR=5.455,95％CI:3.767～7.782,P=0.001)、IL-17(OR=3.489,95％CI:1.038～3.525,P=0.021)、TNF-α(OR=3.210,95％CI:1.852～5.361,P=0.031)及脓毒症(OR=3.051,95％CI:1.341～5.178,P=0.038)、窒息(OR=3.378,95％CI:1.209～5.687,P=0.025)是新生儿发生 ARDS 的影响因素.结论 BALF IL-6、IL-17、TNF-α水平升高,SP-A、SP-D水平降低,伴脓毒症、窒息的新生儿ARDS发生风险较高;监测BALF炎性因子及SP-A、SP-D水平有助于评估ARDS新生儿病情严重程度和治疗转归.

目的 探讨血清亲环素A(cyclophilin A,CyPA)、CD147水平与早产儿脑损伤(brain injury in premature infants,BIPI)的关系.方法 选取2019年11月 ～2021年7月武汉大学人民医院新生儿重症监护病房(neonatal intensive care unit,NICU)收治的胎龄≤34周早产儿65例,留取生后1、3、7天时血液样本并采用酶联免疫吸附测定法(ELISA)检测血清CyPA、CD147水平.根据颅脑影像学检查结果有无脑损伤及脑损伤性质分为脑室周围白质软化(periventricular leukomalacia,PVL)组、脑室周围-脑室内出血(periventricular hemorrhage-intraventricular hemorrhage,PVH-IVH)组及无脑损伤组.比较3组轻度与重度脑损伤之间早产儿血清CyPA、CD147水平.结果 生后第1、3、7天,PVL组、PVH-IVH组、无脑损伤组早产儿血清CyPA、CD147水平比较,差异均有统计学意义(P均<0.05),各时间点PVL组均最高,无脑损伤组最低,PVH-IVH组居中.PVH-IVH及无脑损伤组生后第1、3、7天,CyPA、CD147水平呈下降趋势(P<0.05),PVL组CyPA、CD147水平生后第1天最高,生后第3天与第7天比较,差异无统计学意义(P>0.05).生后第1、3、7天,重度PVH-IVH组及重度PVL组血清CyPA、CD147水平均明显高于轻度组(P均<0.05).CyPA与CD147呈显著正相关.结论 血清CyPA、CD147水平有望成为早期预测BIPI的敏感标志物,有助于评估BIPI的严重程度.

微小RNA(miRNAs,miR)是一类调控基因转录后水平的非编码单链RNA分子,参与不同的生理过程,包括细胞增殖、分化及凋亡等.MiR-155作为miRNAs家族中的重要成员之一,作用广泛,与各类炎症反应均密切相关.大量实验结果和临床数据揭示了miR-155功能的多样性及在中枢神经系统炎症疾病发生和发展中的作用机制.本文就miR-155在常见的几种中枢神经系统炎症疾病中的潜在作用和参与调控的靶点进行综述.

The present research was designed to examine the effects of disintegrin metalloproteinases 10 (ADAM10) on the doxorubicin (DOX)-induced dilated cardiomyopathy (DCM) and the mechanisms involved, with a focus on ADAM10-dependent cleavage of N-cadherin. The present study constructed recombinant lentiviral vectors expressing short hairpin RNA (shRNA) targeting the ADAM10 gene. H9C2 cells were treated with the recombinant lentivirus or GI254023 (an ADAM10 inhibitor). The expression level of N-cadherin and its C-terminal fragment1 (CTF1) was tested by western blotting and flow cytometry. The adhesion ability was analyzed using a plate adhesion model. Cardiac function and morphology were assessed in control and lentivirus-transfected rats with or without DOX treatment. The inhibition of ADAM10 activity significantly increased the expression of full-length N-cadherin on the cellular surface and reduced CTF1 generation in vivo and in vitro . The adhesion ability was also increased in ADAM10-knockdown H9C2 cells. Furthermore, DOX-induced myocardial dysfunction was ameliorated in rats transfected with ADAM10-shRNA lentivirus. These findings demonstrated that ADAM10 specifically cleaves N-cadherin in cardiomyocytes. ADAM10-induced N-cadherin cleavage results in changes in the adhesive behavior of cells. Therefore, ADAM10 may serve as a therapeutic target to reverse cardiac remodeling in DCM.

目的 探讨维生素D、维生素D结合蛋白(vitamin D binding protein,DBP)和炎性因子与早产儿急性呼吸衰竭的关系.方法 选取2018年9月～2019年3月,武汉大学人民医院新生儿科重症监护病房(neonatal intensive care unit,NICU)收治的92例早产儿,胎龄＜34周,体重＜2.0kg.根据早产儿入院后是否发生呼吸衰竭(neonatal respiratory failure,NRF)分为呼吸衰竭组(NRF组)和对照组.所有患儿均在出生24h内静脉取血并采用双抗体夹心酶联免疫分析法(ELISA)检测维生素D、DBP和炎性因子(PCT、IL-6和TNF-α)水平.结果 与对照组比较,NRF组患儿25OHD3、DBP水平均降低(P＜0.05),PCT和IL-6水平明显升高(P＜0.05);且NRF组25OHD3总缺乏率为80％,明显高于对照组,差异有统计学意义(P＜0.05);相关性分析显示NRF组25OHD3与PCT、IL-6水平呈负相关;早产儿出生时25OHD3升高是NRF的保护因素;新生儿呼吸窘迫综合征(NRDS)、新生儿肺炎、新生儿败血症合并炎性因子水平升高均是NRF的危险因素;DBP与NRF和25OHD3无相关性.结论 早产儿静脉血25OHD3,DBP有望成为早期预测NRF的临床新指标,对早产儿进行维生素D水平的早期监测具有重要意义.

目的:建立超高效液相色谱-串联质谱（UPLC-MS/MS）方法检测血浆咖啡因浓度，评价咖啡因药物浓度监控（TDM）在早产儿呼吸窘迫综合征（RDS）治疗中的临床应用价值。方法:取血浆样本于离心管中，加入咖啡因氘代同位素内标，再加入蛋白沉淀剂，充分涡旋混合后，离心取上层清液进入质谱分析。流动相为甲醇和水，梯度洗脱；柱温45 ℃，使用岛津LC-30AD-CL液相系统和AB SCIEX 4500 QTRAP质谱仪建立方法，并对该方法的敏感度、特异度、线性、准确度、不精密度、基质效应、携带污染进行评估。纳入2021年2至4月就诊于武汉大学人民医院新生儿科诊断为新生儿RSD的患者30例，检测不同RDS早产儿相同给药方案下的咖啡因谷值浓度以评估个体变异对咖啡因药物浓度的影响。结果:咖啡因的检出限为0.02 μg/ml，最低定量限为0.05 μg/ml，在1.0~100.0 μg/ml浓度范围内表现出良好的线性（ R2=0.998 6， R>0.99）、特异度（回收率85.52%~114.12%）、准确度（回收率85.97%~114.53%）、日内和日间不精密度（ CV 6.01%~11.28%），基质效应和携带污染可忽略不计。检测30例RSD早产儿相同给药方案（10 mg/kg）后的咖啡因谷值浓度为（25.45±11.61）μg/ml，变异系数为44.88%。 结论:成功建立了一种UPLC-MS/MS方法用于监测咖啡因血药浓度。咖啡因TDM具有一定的临床应用价值，可用于辅助RDS诊疗，提高咖啡因疗效。

目的 探讨早产儿呼吸窘迫综合征(respiratory distress syndrome,RDS)患儿血清维生素A、25羟维生素D3[25-hydroxyvitamin D3,25(OH)D3]水平变化,分析早产儿发生RDS的危险因素.方法 196例早产儿,发生RDS者156例为RDS组,未发生RDS者40例为对照组.比较2组一般资料以及血清维生素A、25(OH)D3水平;多因素logistic回归分析早产儿发生RDS的危险因素.结果 RDS组胎龄[(33.88±1.71)周]、出生体质量[(2.21±0.46)kg]、Apgar评分[(7.43±1.18)分]、血清维生素A[(0.53±0.14)μmol/L]及25(OH)D3[(64.27±36.78) nmol/L]水平低于对照组[(34.81±2.02)周、(2.53±0.52) kg、(7.90±1.58)分、(0.60±0.16)μmol/L、(87.59±44.21)nmol/L](P＜0.05),新生儿窒息、维生素A缺乏、维生素D缺乏发生率(39.74％、73.72％、46.15％)高于对照组(15.00％、57.50％、25.00％)(P＜0.05),男性比率及母亲剖宫产、妊娠期糖尿病、妊娠期高血压比率(61.53％、76.92％、19.87％、19.87％)与对照组(57.50％、72.50％、12.50％、17.50％)比较差异均无统计学意义(P＞0.05).多因素logistic回归分析结果显示,维生素A缺乏(OR=0.405,95％CI:0.187～0.875,P=0.021)、维生素D缺乏(OR=0.345,95％ CI:0.152～0.781,P=0.011)是早产儿发生RDS的危险因素.结论 维生素A、维生素D缺乏与早产儿RDS发生有关.