Off-label use of Baricitinib improves moderate and severe atopic dermatitis in China through inhibiting MAPK and PI3K/Akt/mTOR pathway via targeting JAK-STAT signaling of CD4+ cells.

As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of patients with moderate and severe AD was hyperactive. Among the 49 known immunotherapy targets, JAK1 and JAK2 genes on lymphocytes of AD patients were significantly upregulated, which was closely related to the symptom severity in moderate and severe AD patients. Baricitinib can improve immune hyperresponsiveness and clinical symptoms in moderate and severe AD by inhibiting the activation of Th2 cell subsets and the secretion of Th2-type cytokines through MAPK, mTOR and PI3K-Akt signaling pathways, providing an important theoretical basis for clinical off-label use of Baricitinib to treat moderate and severe AD.

Prehospital ultrasound scanning for abdominal free fluid detection in trauma patients: a systematic review and meta-analysis.

INTRODUCTION: Focused assessment with sonography for trauma helps detect abdominal free fluid. Prehospital ultrasound scanning is also important because the early diagnosis of hemoperitoneum may reduce the time to definitive treatment in the hospital. This study investigated whether prehospital ultrasound scanning can help detect abdominal free fluid. MATERIALS AND METHODS: In this systematic review, relevant databases were searched for studies investigating prehospital ultrasound examinations for abdominal free fluid in trauma patients. The prehospital ultrasound results were compared with computed tomography, surgery, or hospital ultrasound examination data. The pooled sensitivity and specificity values were analyzed using forest plots. The overall predictive power was calculated by the summary receiver operating characteristic curve. The quality of the included studies was assessed using the quality assessment of diagnostic accuracy studies tool. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was performed to assess the certainty of evidence. RESULT: This meta-analysis comprised six studies that included 1356 patients. The pooled sensitivity and specificity values were 0.596 (95% confidence interval [CI] = 0.345-0.822) and 0.970 (95% CI = 0.953-0.983), respectively. The pooled area under the summary receiver operating characteristic curve was 0.998. The quality assessment tool showed favorable results. In the GRADE analysis, the quality of evidence was very low for sensitivity and high for specificity when prehospital ultrasound was used for hemoperitoneum diagnosis. CONCLUSION: The specificity of abdominal free fluid detection using prehospital ultrasound examinations in trauma patients was very high.

Cross-sectional association between red blood cell distribution width and regional cerebral tissue oxygen saturation in preterm infants in the first 14 days after birth.

Background: Hypoxia can threaten the metabolic functions of different systems in immature neonates, particularly the central nervous system. The red blood cell distribution width (RDW) has recently been reported as a prognostic factor in neurologic diseases. Herein, we examined the correlation between RDW and regional cerebral tissue oxygen saturation (rcSO2). Methods: This cross-sectional study included 110 preterm infants born at a gestational age (GA) of <32 weeks, or with a birth weight (BW) of <1,500 g at our institution between January and June 2,022. The rcSO2 was monitored using near-infrared spectroscopy, and RDW was extracted from the complete blood count during the first 14 days after birth. RDW and rcSO2 measurements were analyzed using a cross-sectional research method. Results: We divided the study population into two groups, with a mean rcSO2 value over the first 14 days. Fifty-three preterm had rcSO2 ≥ 55% and 57% < 55%. The 14-days-mean in the study population showing an association of lower rcSO2 values with higher RDW values. Significantly higher RDW values were observed in the low rcSO2 group compared with those in the high rcSO2 group. Threshold effect analysis showed that rcSO2 decreased with RDW values ≥18% (ß, -0.03; 95% CI, -0.04 and -0.02; p ≥ 0.0001). After adjusting for potential confounders, an RDW of ≥18% was determined as the predictive cutoff value for preterm infants with low rcSO2 (Model I: OR, 3.31; 95% CI, 1.36-8.06; p = 0.009; and Model II: OR, 3.31; 95% CI, 1.28-8.53; p = 0.013). Conclusions: An RDW of ≥18% in the first 14 days is associated with rcSO2 of <55% in preterm infants.

The Coronary Reperfusion Effect and Safety of Prehospital P2Y12 Inhibitor in Primary-PCI STEMI Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The concept of early administration of P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) is widely accepted, but whether prehospital administration results in greater coronary reperfusion remains unclear. Our study aims to analyze the benefit and safety of prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor administration. METHOD: Three databases (PubMed, EMBASE, and Cochrane Library) were searched from database inception to June 2023. We included all types of studies except for conference publications, abstract presentations, reviews, and case reports. The primary outcomes were pre-PCI TIMI flow grade 2-3 (TIMI = Thrombolysis in Myocardial Infarction) and major bleeding. The secondary outcomes included post-PCI TIMI flow grade 2-3, major adverse cardiac events (MACE), recurrent myocardial infarction (MI), and short-term (30-day) mortality. RESULT: Eight individual studies with a total of 10823 patients were included in our meta-analysis. Compared with in-hospital P2Y12 inhibitor, prehospital P2Y12 inhibitor were associated with significantly higher rates of pre-PCI TIMI flow grade 2-3 (OR 1.32, 95% CI: 1.09-1.61, p = 0.005) and post-PCI TIMI flow grade 2-3 (OR 1.43, 95% CI: 1.04-1.97, p = 0.03), and a significantly lower risk of recurrent MI (OR 0.69, 95% CI: 0.49-0.96, p = 0.03). There were no significant difference in the risk of major bleeding (OR 1.00, 95% CI: 0.75-1.32, p = 0.98), MACE (OR 0.94, 95% CI: 0.70-1.25, p = 0.65), or short-term mortality (OR 0.87, 95% CI: 0.50-1.51, p = 0.61). CONCLUSION: Prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor is associated with a significantly higher rate of pre-PCI and post-PCI TIMI flow grade 2-3, a reduced risk of recurrent MI, and no increase in major bleeding in STEMI patients undergoing primary PCI.

Risk factors for periventricular-intraventricular haemorrhage severity in preterm infants: a propensity score-matched analysis.

BACKGROUND: Most previous studies comparing etiological studies in infants with and without periventricular-intraventricular haemorrhage (PV-IVH) concluded that younger gestational age (GA) was associated with a higher prevalence rate of PV-IVH. However, only a few studies have examined the risk factors associated with the severity of PV-IVH after removing the influence of GA. Therefore, we investigated the risk factors apart from GA for PV-IVH severity in preterm infants less than 28 weeks. METHODS: This was a retrospective case-control study of preterm infants born in West China Second Hospital with PV-IVH between 2009 and 2020. PV-IVH was defined using cranial ultrasound screening. Preterm infants were divided into no PV-IVH and PV-IVH groups, and preterm infants with PV-IVH were divided into mild and severe PV-IVH groups. Groups were matched in a 1:1 ratio using propensity score calculated from GA. Variables were collected from infant-mother pairs. A stepwise forward multivariate logistic regression model was adopted to select factors that affected PV-IVH in preterm infants. RESULTS: A total of 429 preterm infants were included. The total incidence of PV-IVH in preterm infants was 55.6%, and the incidence of mild and severe PV-IVH was 28.7% and 26.9%, respectively. We matched 162 infants with no PV-IVH with 162 infants with PV-IVH. The results suggested that electrolyte disorder (OR 2.79, 95% CI: 1.34-5.77), early-onset sepsis (OR 1.76, 95% CI: 1.01-3.08), thrombocytopenia (OR 2.87, 95% CI: 1.10-7.48), invasive mechanical ventilation (OR 4.21, 95% CI: 1.86-9.55), and male sex (OR 2.16, 95% CI: 1.29-3.60) were independently associated with PV-IVH. Then, we matched 87 infants with mild PV-IVH with 87 infants with severe PV-IVH. The results suggested that electrolyte disorder (OR 2.88, 95% CI: 1.29-6.45), thrombocytopenia (OR 5.73, 95% CI: 1.91-17.14), and invasive mechanical ventilation (OR 10.54, 95% CI: 1.16-95.85) were independently associated with severity of PV-IVH. CONCLUSIONS: Regardless of GA, electrolyte disorder, early-onset sepsis, thrombocytopenia, invasive mechanical ventilation, and male sex contributed to PV-IVH in preterm infants, and electrolyte disorder, thrombocytopenia, and invasive mechanical ventilation contributed to severe PV-IVH. These risk factors may combine to predict the incidence of PV-IVH in preterm infants.

Impaired Cardiomyocyte Maturation Leading to DCM: A Case Report and Literature Review.

Background: The maturation of cardiomyocytes is a rapidly evolving area of research within the field of cardiovascular medicine. Understanding the molecular mechanisms underlying cardiomyocyte maturation is essential to advancing our knowledge of the underlying causes of cardiovascular disease. Impaired maturation can lead to the development of cardiomyopathy, particularly dilated cardiomyopathy (DCM). Recent studies have confirmed the involvement of the ACTN2 and RYR2 genes in the maturation process, facilitating the functional maturation of the sarcomere and calcium handling. Defective sarcomere and electrophysiological maturation have been linked to severe forms of cardiomyopathy. This report presents a rare case of DCM with myocardial non-compaction, probably resulting from allelic collapse of both the ACTN2 and RYR2 genes. Case Presentation: The proband in this case was a four-year-old male child who presented with a recurrent and aggressive reduction in activity tolerance, decreased ingestion volume, and profuse sweating. Electrocardiography revealed significant ST-T segment depression (II, III, aVF V3-V6 ST segment depression >0.05 mV with inverted T-waves). Echocardiography showed an enlarged left ventricle and marked myocardial non-compaction. Cardiac magnetic resonance imaging revealed increased left ventricular trabeculae, an enlarged left ventricle, and a reduced ejection fraction. Whole exome sequencing revealed a restricted genomic depletion in the 1q43 region (chr1:236,686,454-237,833,988/Hg38), encompassing the coding genes ACTN2, MTR, and RYR2. The identified variant resulted in heterozygous variations in these three genes, with the ACTN2 g.236,686,454-236,764,631_del and RYR2 g.237,402,134-237,833,988_del variants being the dominant contributors to the induction of cardiomyopathy. The patient was finally diagnosed with DCM and left ventricular myocardial non-compaction. Conclusions: This study reports a rare case of DCM with myocardial non-compaction caused by the allelic collapse of the ACTN2 and RYR2 genes. This case provides the first human validation of the critical role of cardiomyocyte maturation in maintaining cardiac function and stability and confirms the key findings of previous experimental research conducted by our group. This report emphasizes the connection between genes involved in regulating the maturation of cardiomyocytes and the development of cardiomyopathy.

Association between congenital heart disease and autism spectrum disorders: A protocol for a systematic review and meta-analysis.

BACKGROUND: Congenital heart disease (CHD), the most common heart defect in children, refers to congenital disease with abnormal development of the heart or large blood vessels during the fetal period. The researchers suggest that children with CHD show more obvious neurodevelopmental disorders than children with normal development, and children with CHD may have a higher risk of social interaction and communication disorders. This is similar to the characteristics of children with autism spectrum disorder (ASD). However, the association between type of CHD and ASD is not well understood. This systematic review and meta-analysis will reveal the relationship between type of CHD and ASD. METHODS: We will search the Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure, Wanfang, Chinese Scientific Journals Full text, and China Biology Medicine disc databases using relevant subject terms and free words. We will use a fixed effects model or random effects model for meta-analysis. The risk of bias will be assessed by the Newcastle-Ottawa Scale and the agency for health care research and quality. Heterogeneity will be tested by Q statistics and I² values. Publication bias will be detected by funnel plots and Egger test. Subgroup analyses and sensitivity analyses will also be used to explore and interpret the heterogeneity. RESULTS: The study will afford additional insight into the investigation the association between type of CHD and ASD. CONCLUSIONS: The results will provide evidence for the early identification and early intervention of ASD in children with CHD, which may contribute to improving the neurodevelopmental outcome of children with CHD.

Antenatal infection and intraventricular hemorrhage in preterm infants: A meta-analysis.

BACKGROUND: The aim of this study was to summarize current evidence evaluating the association between antenatal infection and intraventricular hemorrhage (IVH) in preterm infants. MATERIALS AND METHODS: We searched for published articles on antenatal infection and IVH in 3 English (PubMed, the Cochrane Library, and EBSCO) and 3 Chinese (VEIPU, CNKI, and WANFANG) databases on May 19, 2019. In addition, the references of these articles were screened. The included studies had to meet all of the following criteria: preterm infants (<37 weeks); comparing antenatal infection with no infection; the outcomes included IVH (all grades), mild IVH, or sereve IVH; the type of study was randomized controlled trial or cohort study. RESULTS: A total of 23 cohort studies involving 13,605 preterm infants met our inclusion criteria. Antenatal infection increased the risk of IVH (odds ratios ([OR] 2.18, 95% confidence intervals [CI] 1.58-2.99), mild IVH (OR 1.95, 95% CI 1.09-3.49) and severe IVH (OR 2.65, 95% CI 1.52-4.61). For type of antenatal infection, the ORs and 95% CI were as follows: 2.21 (1.60-3.05) for chorioamnionitis, 2.26 (1.55-3.28) for histologic chorioamnionitis, 1.88 (1.22-2.92) for clinical chorioamnionitis, and 1.88 (1.14-3.10) for ureaplasma. CONCLUSIONS: Antenatal infection may increase the risk of developing IVH in the preterm infant. The evidence base is however of low quality and well-designed studies are needed.

Human milk as a protective factor for bronchopulmonary dysplasia: a systematic review and meta-analysis.

OBJECTIVE: To summarise current evidence evaluating the effects of human milk on the risk of bronchopulmonary dysplasia (BPD) in preterm infants. DESIGN: We searched for studies on human milk and BPD in English and Chinese databases on 26 July 2017. Furthermore, the references of included studies were also screened. The inclusion criteria in this meta-analysis were the following: (1) preterm infants (<37 weeks); (2) human milk; (3) comparing with formula feeding; (4) the outcome included BPD; and (5) the type of study was randomised controlled trial (RCT) or cohort study. RESULT: A total of 17 cohort studies and 5 RCTs involving 8661 preterm infants met our inclusion criteria. The ORs and 95% CIs of six groups were as follows: 0.78 (0.68 to 0.88) for exclusive human milk versus exclusive formula group, 0.77 (0.68 to 0.87) for exclusive human milk versus mainly formula group, 0.76 (0.68 to 0.87) for exclusive human milk versus any formula group, 0.78 (0.68 to 0.88) for mainly human milk versus exclusive formula group, 0.83 (0.69 to 0.99) for mainly human milk versus mainly formula group and 0.82 (0.73 to 0.93) for any human milk versus exclusive formula group. Notably, subgroup of RCT alone showed a trend towards protective effect of human milk on BPD but no statistical significance. CONCLUSION: Both exclusive human milk feeding and partial human milk feeding appear to be associated with lower risk of BPD in preterm infants. The quality of evidence is low. Therefore, more RCTs of this topic are needed.

[Current status of the application of 1H-magnetic resonance spectroscopy in neonates with hypoxic-ischemic encephalopathy].

OBJECTIVE: To investigate the current status of the application of 1H-magnetic resonance spectroscopy (1H-MRS) in neonates with hypoxic-ischemic encephalopathy (HIE), and to describe the trend of research in the field. METHODS: PubMed, EMBASE, and Web of Science were searched for English articles published up to January 10, 2018, with the combination of key words and MeSH terms. The articles were screened according to inclusion and exclusion criteria. Excel 2016, Bicomb 2.0, and VOSviewer1.6.6 were used to analyze the key words, to perform a cluster analysis of hot words, and to plot the knowledge map. RESULTS: A total of 66 articles were included, and 27 high-frequency key words were extracted. The results showed that 1H-MRS was mainly used in four directions of the clinical practice and scientific research on HIE. In clinical practice, 1H-MRS attracted wide attention as a clinical examination for HIE and a tool for prognostic evaluation; in scientific research, 1H-MRS was used in animal experiments and studies associated with mild hypothermia therapy. CONCLUSIONS: As an auxiliary means of magnetic resonance imaging, 1H-MRS plays an important role in investigating the pathogenesis of neonatal HIE, improving existing therapies, and evaluating the prognosis of neonates with HIE.

[Protective effect of astrocyte exosomes on hypoxic-ischemic neurons].

OBJECTIVE: To study the effect of astrocyte exosomes on hypoxic-ischemic neurons. METHODS: Rat astrocytes were cultured in vitro, and differential centrifugation was used to obtain the exosomes from the cell supernatant. Transmission electron microscopy, Nanosight, and Western blot were used for the identification of exosomes. BCA method was used to measure the concentration of exosomes. Rat neurons were cultured in vitro and then divided into control group, exosome group, oxygen glucose deprivation (OGD) group, and OGD+exosome group (n=3 each). The OGD and OGD+exosome groups were cultured in glucose-free medium under the hypoxic condition. The exosome and OGD+exosome groups were treated with exosomes at a final concentration of 22 μg/mL. The control and OGD groups were given an equal volume of phosphate-buffered saline. ELISA was used to measure the level of lactate dehydrogenase (LDH) in neurons. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure the apoptotic index of neurons. RESULTS: The identification of exosomes showed that the exosomes extracted by differential centrifugation had the features of exosomes. Compared with the control and exosome groups, the OGD group had significant increases in LDH level and apoptotic index (P<0.05). Compared with the OGD group, the OGD+exosome group had significant reductions in LDH level and apoptotic index (P<0.05). CONCLUSIONS: The exosomes from astrocytes have a protective effect on neurons with hypoxic-ischemic injury.

Association among obesity, overweight and autism spectrum disorder: a systematic review and meta-analysis.

Obesity, overweight and autism spectrum disorder (ASD) remain serious public health problems. Although lots of studies have recently explored the association among obesity, overweight and ASD, the findings are inconsistent. Thus, we conducted a meta-analysis of epidemiological studies to examine the association among obesity, overweight and ASD. PubMed, Embase, and the Cochrane Library were used for literature searches to identify eligible studies published in English before November 15, 2016. Relevant studies estimating the association among obesity, overweight and ASD were included. Fifteen studies encompassing 49,937,078 participants and 1,045,538 individuals with ASD were included in this study. A random effects model was chosen to synthesize the effect sizes of individual studies. The prevalence of obesity was significantly higher in individuals with ASD than in controls (OR = 1.84, 95% confidence interval [CI]: 1.37-2.48, P < 0.001). However, the prevalence of overweight in individuals with ASD was not significantly different from that in controls (OR = 1.07, 95% CI: 0.83-1.38, P = 0.62). Both sensitivity analysis and publication bias testing revealed that the findings were robust. The meta-analysis showed a significant association between obesity and ASD. However, no significant association was identified between overweight and ASD.

[Protective effect of exosome on organs after ischemia-reperfusion injury].

Objective: To investigate the protective effect of the exosome on the organ damage induced by ische-mia-reperfusion (I/R) so as to provide a new way for the treatment of I/R damage. Methods: The literature related to the treatment of I/R damage was reviewed and analyzed. Results: The exosome volume is small and it is present in blood, cerebrospinal fluid, and urine, which has the function to cross the blood-brain barrier, and protect the heart, brain and other organs after I/R damage. Conclusion: Exosome is a new material for the treatment of I/R organ injury, and it is important to understand the protective effect and possible mechanism.