Alteration of gut microbiota in Henoch-Schönlein purpura children with gastrointestinal involvement.

BACKGROUND: The compositional and structural changes of gut microbiota were closely related to the status of Henoch-Schönlein purpura (HSP). AIMS: To investigate if clinical indicators and gut microbiota differ between HSP patients with or without gastrointestinal (GI) involvement and to explore the alterations of fecal microbiota in HSP children with and without GI symptoms. METHODS: A total of 22 children with HSP were enrolled in the study. Fecal microbiota composition was analyzed by 16S rRNA sequencing. Clinical indicators, fecal microbial diversity, and compositions were compared between the two groups. RESULTS: Respectively, 9 patients with GI involvement (HSP-A) and 13 patients without GI involvement (HSP-N) were enrolled. Prealbumin (PA) and the ratio of immunoglobulin A (IgA) / complement (C)3 were significantly decreased in the HSP-A group and an elevated D-dimer was found in the HSP-N group. The relative abundances of Blautia, Lachnospira, and Haemophilus were significantly higher in the HSP-A group compared to HSP-N. Lower levels of unidentified Prevotellaceae, Parabacteroides, and Romboutsia were found in HSP-A patients. The linear discriminant analysis effect size (LEfSe) showed that the biomarkers for the HSP-A group included Blautia, Anaerostipes, Veillonella, Lachnospira, and Haemophilus. For the HSP-N group, unidentified Prevotellaceae, Intestinibacter, Romboutsia, and Akkermansia were the prominent biomarkers at the genus level. Additionally, the ratio of IgA/C3 exhibited a negative correlation with the genus Blautia. Meanwhile, PA showed negatively correlation with Veillonella. CONCLUSIONS: These results provide a broader understanding for future microbial-based therapies to decrease the development of GI involvement and improve the clinical outcome of HSP in children.

Effects of percutaneous endovascular angioplasty for severe stenosis or occlusion of subclavian artery.

To investigate the effect and safety of percutaneous endovascular angioplasty (PEA) with optional stenting for the treatment of severe stenosis or occlusion of subclavian artery, patients with severe stenosis ≥ 70% or occlusion of subclavian artery treated with PEA were retrospectively enrolled. The clinical data were analyzed. A total of 222 patients were retrospectively enrolled, including 151 males (68.0%) and 71 females (32.0%) aged 48-86 (mean 63.9 ± 9.0) years. Forty-seven (21.2%) patients had comorbidities. Subclavian artery stenosis ≥ 70% was present in 201 (90.5%) patients and complete subclavian occlusion in 21 (9.5%) cases. Angioplasty was successfully performed in all (100%) patients. Balloon-expandable stents were used in 190 (85.6%) cases, and self-expandable stents in 20 (9.0%) cases. Only 12 (5.4%) cases were treated with balloon dilation only. Among 210 patients treated with stent angioplasty, 71 (33.8% or 71/210) cases underwent balloon pre-dilation, 139 (66.2% or 139/210) had direct deployment of balloon-expandable stents, and 2 (1.0% or 2/210) experienced balloon post-dilation. Distal embolization protection devices were used in 5 (2.3% or 5/222) cases. Periprocedural complications occurred in 3 (1.4%) patients, including aortic dissection in 2 (0.9%) cases and right middle cerebral artery embolism in 1 (0.5%). No hemorrhage occurred. Among 182 (82.0%) patients with 6-month follow-up, restenosis > 70% occurred in 1 (0.5%) patient, and among 68 (30.6%) patients with 12-month follow-up, restenosis > 70% took place in 11 (16.2%) patients. Percutaneous endovascular angioplasty can be safely and efficiently performed for the treatment of severe stenosis ≥ 70% or occlusion of subclavian artery.

Checkpoint Kinase 1 Stimulates Endogenous Cardiomyocyte Renewal and Cardiac Repair by Binding to Pyruvate Kinase Isoform M2 C-Domain and Activating Cardiac Metabolic Reprogramming in a Porcine Model of Myocardial Ischemia/Reperfusion Injury.

BACKGROUND: The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. METHODS AND RESULTS: Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming. CONCLUSIONS: This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.

Significance of atherosclerotic plaque location in recanalizing non-acute long-segment occlusion of the internal carotid artery.

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.

CT-based radiomics analysis of different machine learning models for differentiating gnathic fibrous dysplasia and ossifying fibroma.

OBJECTIVE: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery. MATERIALS AND METHODS: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value. RESULTS: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy. CONCLUSION: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making.

Prediction model for spinal cord injury in spinal tuberculosis patients using multiple machine learning algorithms: a multicentric study.

Spinal cord injury (SCI) is a prevalent and serious complication among patients with spinal tuberculosis (STB) that can lead to motor and sensory impairment and potentially paraplegia. This research aims to identify factors associated with SCI in STB patients and to develop a clinically significant predictive model. Clinical data from STB patients at a single hospital were collected and divided into training and validation sets. Univariate analysis was employed to screen clinical indicators in the training set. Multiple machine learning (ML) algorithms were utilized to establish predictive models. Model performance was evaluated and compared using receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration curve analysis, decision curve analysis (DCA), and precision-recall (PR) curves. The optimal model was determined, and a prospective cohort from two other hospitals served as a testing set to assess its accuracy. Model interpretation and variable importance ranking were conducted using the DALEX R package. The model was deployed on the web by using the Shiny app. Ten clinical characteristics were utilized for the model. The random forest (RF) model emerged as the optimal choice based on the AUC, PRs, calibration curve analysis, and DCA, achieving a test set AUC of 0.816. Additionally, MONO was identified as the primary predictor of SCI in STB patients through variable importance ranking. The RF predictive model provides an efficient and swift approach for predicting SCI in STB patients.

Effect of early preventive supplementation with calcium and phosphorus on metabolic bone disease in premature infants.

OBJECTIVE: The objective was to study the effect of early preventive calcium and phosphorus supplementation on metabolic bone disease in preterm infants. METHODS: A retrospective analysis of 234 preterm infants with a gestational age < 32 weeks or birth weight < 1500 g who were hospitalized in the Neonatology Department of the Second Hospital of Shandong University from 01.2018 to 12.2020 was conducted. One hundred thirty-two premature infants hospitalized from 01.2018 to 06.2019 did not receive prophylactic calcium and phosphorus supplementation in the early postnatal period. These infants received calcium or phosphorus supplementation at the time of hypocalcaemia or hypophosphatemia diagnosis. One hundred two premature infants hospitalized from 07.2019 to 12.2020 received early preventive calcium and phosphorus supplementation after birth. The levels of serum calcium and phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, calcitonin, and parathyroid hormone at different time points and growth indicators at six months of age were compared between the two groups of infants. The number of cases of metabolic bone disease and fracture between the two groups was compared. RESULTS: 1) A total of 12 infants (5.13%) among the 234 preterm infants were diagnosed with metabolic bone disease, including 2 (1.96%) in the prophylactic supplementation group and 10 (7.58%) in the nonprophylactic supplementation group. Fractures occurred in 3 premature infants (25.0%) with metabolic bone disease, all of whom were in the group that did not receive prophylactic supplementation. 2) There was no significant difference in serum calcium and calcitonin levels between the two groups. The levels of serum phosphorus and 25 hydroxyvitamin D in the prophylactic supplementation group were higher than those in the nonprophylactic supplementation group (P < 0.05). In comparison, alkaline phosphatase and parathyroid hormone levels were lower in the prophylactic supplementation group than in the nonprophylactic supplementation group (P < 0.05). Preterm infants in the prophylactic supplementation group had higher weight, length, head circumference, and bone density values than those in the nonprophylactic supplementation group (P < 0.05). CONCLUSION: Preventive supplementation with calcium and phosphorus after birth can effectively improve calcium and phosphorus metabolism, and reduce the incidence of metabolic bone disease and fractures in premature infants. This can be further publicized and used clinically.

IL-12-Overexpressed Nanoparticles Suppress the Proliferation of Melanoma Through Inducing ICD and Activating DC, CD8+ T, and CD4+ T Cells.

Purpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO3-polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy. Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80+/CD86+, CD3+/CD4+ and CD3+/CD8+ were analyzed by flow cytometry. Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80+/CD86+ expression of DC from lymph glands, and the number of CD3+/CD8+T or CD3+/CD4+T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor. Conclusion: The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4+ T cell, and enhancing the function of tumor-reactive CD8+ T cells.

m6A-methylated KCTD21-AS1 regulates macrophage phagocytosis through CD47 and cell autophagy through TIPR.

Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.

Site-Specific Deaminative Trifluoromethylation of Aliphatic Primary Amines.

The introduction of trifluoromethyl groups into organic molecules is of paramount importance in modern synthetic chemistry and medicinal chemistry. While methods for constructing C(sp2 )-CF3 bonds have been well established, the advancement of practical and comprehensive approaches for forming C(sp3 )-CF3 bonds remains considerably restricted. In this work, we describe an efficient and site-specific deaminative trifluoromethylation reaction of aliphatic primary amines to afford the corresponding alkyl trifluoromethyl compounds. The reaction proceeds at room temperature with readily accessible N-anomeric amide (Levin's reagent) and bench-stable bpyCu(CF3 )3 (Grushin's reagent, bpy=2,2'-bipyridine) under blue light. The protocol features mild reaction conditions, good functional group tolerance, and moderate to good yields. Remarkably, the method can be applied to the direct, late-stage trifluoromethylation of natural products and bioactive molecules. Experimental mechanistic studies were conducted, and a radical mechanism is proposed, wherein the dual roles of Grushin's reagent have been elucidated.

High-Valence Metal Doping Induced Lattice Expansion for M-FeNi LDH toward Enhanced Urea Oxidation Electrocatalytic Activities.

The precise design of low-cost, efficient, and definite electrocatalysts is the key to sustainable renewable energy. The urea oxidation reaction (UOR) offers a promising alternative to the oxygen evolution reaction for energy-saving hydrogen generation. In this study, by tuning the lattice expansion, a series of M-FeNi layered double hydroxides (M-FeNi LDHs, M: Mo, Mn, V) with excellent UOR performance are synthesized. The hydrolytic transformation of Fe-MIL-88A is assisted by urea, Ni2+ and high-valence metals, to form a hollow M-FeNi LDH. Owing to the large atomic radius of the high-valence metal, lattice expansion is induced, and the electronic structure of the FeNi-LDH is regulated. Doping with high-valence metal is more favorable for the formation of the high-valence active species, NiOOH, for the UOR. Moreover, the hollow spindle structure promoted mass transport. Thus, the optimal Mo-FeNi LDH showed outstanding UOR electrocatalytic activity, with 1.32 V at 10 mA cm-2 . Remarkably, the Pt/C||Mo-FeNi LDH catalyst required a cell voltage of 1.38 V at 10 mA·cm-2 in urea-assisted water electrolysis. This study suggests a new direction for constructing nanostructures and modulating electronic structures, which is expected to ultimately lead to the development of a class of auxiliary electrocatalysts.

Understanding the intention and behavior of psychological help-seeking among Chinese college students using theory of planned behavior: a three-month follow-up study.

Underutilization of mental health services is common and associated with substantial suffering, mental disorders and death. The present study aimed to explore factors significantly affecting the professional psychological help-seeking behavior based on the Theory of Planned Behavior (TPB). A sample of 597 Chinese college students recruited online completed the questionnaires, which measured four constructs of TPB including help-seeking intention, attitude, subjective norm and perceived behavioral control in December 2020. Help-seeking behaviors were evaluated three months later in March 2021. A two-step structural equation modeling procedure was used to test the TPB model. Findings show that partially consistent with TPB, more positive attitudes about seeking professional help (Β = .258, p = .001) and higher perceived behavioral control (Β = .504, p < .001) directly predicted higher intention to seek mental health services, and perceived behavioral control (Β = .230, p = .006) directly predicted help-seeking behavior. However, behavioral intention (Β = -.017, p = .830) did not statistically significantly predict help-seeking behavior, while subjective norm (Β = .047, p = .356) did not predict help-seeking intention as well. The model accounted for 49.9% of the variance modeling help-seeking intention and 12.4% of the variance modeling help-seeking behavior. The results revealed the importance of attitude and perceived behavioral control in predicting help-seeking intention and behavior among Chinese college students and indicated that there existed a gap between intention and actual help-seeking behavior.

A screened predictive model for esophageal squamous cell carcinoma based on salivary flora data.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the digestive system in the esophageal squamous epithelium. Many studies have linked esophageal cancer (EC) to the imbalance of oral microecology. In this work, different machine learning (ML) models including Random Forest (RF), Gaussian mixture model (GMM), K-nearest neighbor (KNN), logistic regression (LR), support vector machine (SVM) and extreme gradient boosting (XGBoost) based on Genetic Algorithm (GA) optimization was developed to predict the relationship between salivary flora and ESCC by combining the relative abundance data of Bacteroides, Firmicutes, Proteobacteria, Fusobacteria and Actinobacteria in the saliva of patients with ESCC and healthy control. The results showed that the XGBoost model without parameter optimization performed best on the entire dataset for ESCC diagnosis by cross-validation (Accuracy = 73.50%). Accuracy and the other evaluation indicators, including Precision, Recall, F1-score and the area under curve (AUC) of the receiver operating characteristic (ROC), revealed XGBoost optimized by the GA (GA-XGBoost) achieved the best outcome on the testing set (Accuracy = 89.88%, Precision = 89.43%, Recall = 90.75%, F1-score = 90.09%, AUC = 0.97). The predictive ability of GA-XGBoost was validated in phylum-level salivary microbiota data from ESCC patients and controls in an external cohort. The results obtained in this validation (Accuracy = 70.60%, Precision = 46.00%, Recall = 90.55%, F1-score = 61.01%) illustrate the reliability of the predictive performance of the model. The feature importance rankings obtained by XGBoost indicate that Bacteroides and Actinobacteria are the two most important factors in predicting ESCC. Based on these results, GA-XGBoost can predict and diagnose ESCC according to the relative abundance of salivary flora, providing an effective tool for the non-invasive prediction of esophageal malignancies.

Transradial intra-aortic catheter looping in the angioplasty of severe intracranial symptomatic arteriosclerotic diseases.

Purpose: This study aims to investigate the effect and feasibility of intra-aortic catheter looping via transradial access in angioplasty for symptomatic intracranial severe (>70%) atherosclerotic stenosis or occlusion of large arteries (SISOLAs). Materials and methods: Patients with SISOLAs who underwent transradial endovascular angioplasty using the catheter looping technique in the ascending aorta were retrospectively enrolled. The clinical data and treatment outcomes were analyzed. Results: Fifteen patients aged 48-71 years were enrolled in this study. Left vertebrobasilar artery occlusion was present in 1 (6.7%) patient, severe left middle cerebral artery stenosis in 7 (46.7%) patients, severe left internal carotid artery (ICA) stenosis of the ophthalmic segment in 4 (26.7%) patients, severe left ICA stenosis of the cavernous segment in 2 (13.3%) patients, and severe right middle cerebral artery stenosis in 2 (13.3%) patients. The arterial stenosis ranged from 70 to 92% (mean 86%) before stenting. The looping of a guiding catheter in the ascending aorta via transradial access for angioplasty was successful in all patients (100%). The vertebral artery intracranial segment occlusion was successfully recanalized, while severe stenosis in the remaining 14 patients was successfully eliminated. After endovascular recanalization, the residual stenosis was reduced by 12-26% (median 18%). No puncture-related complications or surgical-related neurological complications occurred in these patients. In the follow-up angiography conducted on 10 (66.7%) patients after 6-25 months, no in-stent restenosis was detected. Conclusion: Intra-aortic guiding catheter looping via transradial access for endovascular angioplasty of SISOLAs is technically safe, feasible, and effective, especially when the transfemoral artery approach is difficult or impossible to undertake.

Age and sex-specific differences of mindfulness traits with measurement invariance controlled in Chinese adult population: A pilot study.

Objectives: To examine the relationships of age and sex with mindfulness traits among Chinese adults with controlling for measurement invariance. Methods: A total of 1777 participants completing the Five-Facet Mindfulness Questionnaire were included for analysis. Their age and sex information were also collected. Descriptive analysis, Pearson's Chi-Square test and analysis of variance were performed to test the age- and sex-specific differences, measurement invariance was examined by confirmatory factor analysis. Results: Excellent data fit to the model indicated configural, metric, and scalar invariance across age and sex. Participants aged 60 or above scored significantly higher in dimensions of acting with awareness, nonjudging of inner experience, nonreactivity to inner experience, and the total scores than younger individuals, who had higher scores in the observing domain. In addition, females scored higher in describing and observing than males, while the latter had higher score in nonreactivity to inner experience. Conclusions: The Five-Facet Mindfulness Questionnaire Mindfulness showed acceptable measurement invariance across age and sex in Chinese adult population. The old and the young differs in the traits of awareness, observing, nonjudging of inner experience, nonreactivity to inner experience and the total mindfulness level, while males and females varied in describing, observing and nonreactivity to inner experience. Individual differences should be considered and well addressed in future studies on mindfulness.

[Interpretation of the key updates in the 2022 European guideline on the management of neonatal respiratory distress syndrome]. / 2022年欧洲新生儿呼吸窘迫综合征管理指南更新要点解读.

With the deepening of clinical research, the management of neonatal respiratory distress syndrome (RDS) needs to be optimized and improved. This article aims to introduce the 2022 European guideline on the management of neonatal RDS, focusing on its key updates. The guide has optimized the management of risk prediction for preterm birth, maternal referral, application of prenatal corticosteroids, application of lung protective ventilation strategies, and general care for infants with RDS. The guideline is mainly applicable to the management of RDS in neonates with gestational age greater than 24 weeks.

Adenoid Ameloblastoma Shares Clinicopathologic, Immunohistochemical, and Molecular Features With Dentinogenic Ghost Cell Tumor: A Comparative Analysis.

The updated classification of odontogenic tumors by the World Health Organization (WHO) has included adenoid ameloblastoma (AA) as a distinct entity. However, distinguishing between AA and dentinogenic ghost cell tumor (DGCT) can still be challenging due to their significant morphologic similarities. In this study, we aimed to compare the clinicopathologic, immunohistochemical, and molecular characteristics of AA and DGCT to aid in their differentiation and to shed light on their pathologic mechanisms. Thirteen cases of AA and 14 cases of DGCT (15 samples) were analyzed, along with 11 cases of adenomatoid odontogenic tumor (AOT) and 18 cases of conventional ameloblastoma (AM) for comparative purposes. The study found that AA and DGCT shared a similar long-term prognosis. Immunohistochemically, all cytokeratins detected, except CK8/18, were not statistically significant in differentiating AA and DGCT, while there was a statistically significant difference in the immunophenotype of CK7 and CK10/13 between AA and AM. Nuclear ß-catenin accumulation were detected in all cases of AA and DGCT, while AOTs and AMs exhibited cytoplasmic ß-catenin. Molecularly, CTNNB1 hotspot mutations were found in only 1 case of AA (1/13), but not found in the other 3 types of tumors. BRAF p.V600E mutation was positive in 2/13 (15%) AA, 1/15 (7%) DGCT, and 2/11 (18%) AOT cases. In comparison, conventional AM was positive for BRAF p.V600E mutation in 94% (17/18) of cases, while KRAS mutations were detected in 63% (7/11) of AOT cases. The study suggests that the so-called AA is a rare benign tumor that exhibits clinical, immunohistochemical, and molecular features similar to DGCTs. Based on these findings, AA should not be categorized as a standalone entity solely based on the presence of whorls/morules and cribriform/duct-like structures. Further studies are needed to investigate the pathologic mechanisms of these tumors and to identify potential therapeutic targets.

Indirubin-3'-oxime promotes the efficacy of GnRHa in obese-induced central precocious puberty and maintains normal bone growth and body weight via the ERK-Sp1-KISS-1/GPR54 axis.

Central precocious puberty (CPP) is a widespread developmental abnormality. The application of gonadotrophin-releasing hormone agonist (GnRHa) is widely useful for the medical therapy of CPP. This study aimed to investigate the combination effect and mechanism of indirubin-3'-oxime (I3O), an active ingredient analogue of traditional Chinese medicine, and GnRHa treatment on the progression of CPP. First, female C57BL/6 mice were fed with a high-fat diet (HFD) for the induction of precocious puberty and treated with GnRHa and I3O alone or in combination. Development of sexual maturation, bone growth and obesity were determined by vaginal opening detection, H&E staining and ELISA. The protein and mRNA expression levels of related genes were evaluated via western blotting, immunohistochemical method and RT-qPCR. Subsequently, tBHQ, an inhibitor of ERK, was applied to verify whether the mechanism of I3O was associated with this signaling. The results showed that the treatment of I3O alone or in combination with GnRHa could alleviate the HFD-induced earlier vaginal opening and serum levels of the gonadal hormone in mice. And, I3O could significantly eliminate the role of growth deceleration of GnRHa in bone development and reversed the side effect of GnRHa on body weight. More importantly, we found that I3O decreased the expression of KISS-1 and GPR54 by suppressing the phosphorylation of ERK1/2 and Sp1 in the hypothalamus in mice. In summary, these data indicated that I3O could promote the efficacy of GnRHa in HFD-induced precocious puberty, and maintain bone growth and body weight in mice via the ERK-Sp1-KISS-1/GPR54 axis.

Transradial access with intra-aortic catheter looping for the treatment of intracranial aneurysms.

Purpose: The study aimed to investigate the feasibility and effect of transradial access with intra-aortic catheter looping for the treatment of intracranial aneurysms. Materials and methods: This retrospective one-center study was performed on patients with intracranial aneurysms which were embolized through transradial access with intra-aortic catheter looping because of the difficulty of transfemoral access or transradial access without intra-aortic catheter looping. The imaging and clinical data were analyzed. Results: A total of 11 patients were enrolled, including seven (63.6%) male patients. Most patients were associated with one or two risk factors of atherosclerosis. There were nine aneurysms in the left internal carotid artery system and two aneurysms in the right internal carotid artery system. All 11 patients had complications with different anatomic variations or vascular diseases, which made endovascular operation via the transfemoral artery difficult or a failure. The right transradial artery approach was adopted in all patients, and the success rate of intra-aortic catheter looping was 100%. Embolization of intracranial aneurysms was successfully completed in all patients. No instability of the guide catheter was encountered. No puncture site complications or surgical-related neurological complications occurred. Conclusion: Transradial access with intra-aortic catheter looping for embolization of intracranial aneurysms is technically feasible, safe, and efficient as an important supplementary approach to the routine transfemoral access or transradial access without intra-aortic catheter looping.

Deaminative bromination, chlorination, and iodination of primary amines.

The primary amino group has been seldom utilized as a transformable functionality in organic synthesis. Reported herein is a deaminative halogenation of primary amines using N-anomeric amide as the nitrogen-deletion reagent. Both aliphatic and aromatic amines are competent substrates for direct halogenations. The mildness and robustness of the protocol are evidenced by the successful reactions of several complex- and functional group-enriched bioactive compounds or drugs. Elaboration of the resulting products provides interesting analogues of drug molecules.