Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

A multicentre randomized double-blind placebo-controlled phase III study of the efficacy and safety of xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials. OBJECTIVES: To evaluate the efficacy and safety of xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated. RESULTS: At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and 3.6% of patients in the placebo group. PASI 75 and PGA 0/1 were maintained until week 52. No unexpected adverse events were recorded. CONCLUSIONS: Xeligekimab showed high efficacy and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

Psoriasis is a skin disease characterized by scaly and raised patches of skin on any part of the body. The condition can be caused by a combination of how a person's immune system works, their genes and their environment. A cytokine is a substance secreted by certain cells of the immune system that have an effect on other cells. One such cytokine, called IL-17A, has been associated with different inflammatory diseases, including psoriasis. We conducted a large trial in Chinese people with moderate-to-severe psoriasis to look at the efficacy (ability to produce the intended result) and safety of a medicine called xeligekimab (known as a 'monoclonal antibody') which works by targeting IL-17A. We randomly assigned 420 Chinese patients to receive 200 mg of xeligekimab every 2 weeks or a 'placebo' (no active medicine) for the first 12 weeks. We extended the treatment schedule of xeligekimab to every 4 weeks for a further 40 weeks. To assess how the medicine worked, we measured people's psoriasis symptoms and severity. To assess how safe the medicine was, we looked at the side-effects (or 'adverse events'). The results of this trial showed that xeligekimab improved people's psoriasis and itching starting at week 4 of receiving treatment, and more than 60% of people achieved improvement or remission by week 6, which was sustained up to week 52. The safety of xeligekimab was similar to another medicine classed as a monoclonal antibody (called secukinumab) and there were no new or unexpected adverse events reported. Overall, our findings suggest that xeligekimab is a safe and effective medicine for the treatment of psoriasis in Chinese people.

Neuroserpin normalization by mesenchymal stem cell therapy after encephalopathy of prematurity in neonatal rats.

BACKGROUND: Hypoxic-ischemia (HI), infection/inflammation and reperfusion injury are pathogenic factors of encephalopathy of prematurity, which involves maturational/neurotrophic disturbances in oligodendrocyte progenitor cells (OPC) and neurons/axons. Mesenchymal stem cells (MSCs) might facilitate neuroserpin production, which is neurotrophic for OPC/neurons. This study investigated MSC effects on developmental disturbances after lipopolysaccharide (LPS)-sensitized HI/reperfusion (LHIR) injury and the relation to neuroserpin expression. METHODS: Postnatal day 2 (P2) rat pups received intraperitoneal LPS (5 µg/kg) injection followed by HI (unilateral common-carotid-artery ligation and 6.5% oxygen exposure for 90 min) and post-HI reperfusion (release of ligation). MSCs (5 × 104 cells) were injected into the left lateral ventricle at 24 h post-LHIR. Neurological tests and brain tissue examinations were performed between P5 and P56. RESULTS: After LHIR injury, MSC therapy significantly reduced cell death in subplate neurons, attenuated axonal damage, and facilitated synaptophysin synthesis in the cortex. It also alleviated OPC maturation arrest and preserved the complexity of myelinated axons in the white matter, leading to cognitive, motor and behavioral functional improvements. These beneficial effects were linked to restored neuroserpin expression in subplate neurons. CONCLUSIONS: MSC therapy ameliorated developmental disturbances after LHIR injury through protection of neuroserpin expression, serving as a promising approach for treating encephalopathy of prematurity. IMPACT: Neuroserpin is secreted by subplate neurons and may regulate the development of neurons and oligodendrocyte-axon contact for myelination in the premature brain. LPS-sensitized hypoxic-ischemia/reperfusion (LHIR) injury caused the developmental disturbances of neurons/axons and oligodendrocytes, and lowered neuroserpin levels in a neonatal rat model simulating encephalopathy of prematurity. Mesenchymal stem cell therapy alleviated the developmental disturbances after LHIR injury through protection of neuroserpin expression in subplate neurons, offering a new perspective on potential treatment for encephalopathy of prematurity.

The immunomodulatory effects of metformin in LPS-induced macrophages: an in vitro study.

OBJECTIVE: The study aimed to explore the immunomodulatory effects of clinically relevant concentrations of metformin on macrophages during sepsis, which is characterized by an initial hyperinflammatory phase followed by a period of immunosuppression.  METHODS: We employed the RAW 264.7 mouse macrophage cell line as an in vitro model to induce inflammatory responses and immune suppression through primary and secondary stimulation by lipopolysaccharide (LPS). The cells were exposed to clinically relevant concentrations of metformin, and their responses were gauged through cytotoxicity assays, enzyme-linked immunosorbent assay for cytokine quantification, and assessments of intracellular reactive oxygen species (ROS) production. Moreover, to probe the role of AMPK in mediating the effects of metformin, we conducted an AMP-activated protein kinase (AMPK) activity assay and knocked down AMPK using siRNA.  RESULTS: Our study revealed that clinically relevant concentrations of metformin considerably decreased the LPS-induced secretion of tumor necrosis factor-α and interleukin-6, which indicates the suppression of the initial hyperinflammatory response. Furthermore, metformin prevented LPS-induced immunosuppression. Notably, these immunomodulatory effects of metformin were not mediated by the activation of the AMPK pathway, as evidenced by the unaltered AMPK activity and siRNA experiments. The modulation of intracellular ROS levels emerged as the critical mechanism underlying the inhibition of hyperinflammation and impediment of immunosuppression by metformin. CONCLUSION: A certain therapeutic dose of metformin inhibited hyperinflammatory responses and alleviated immunosuppression in LPS-induced macrophages through the bidirectional modulation of intracellular ROS generation.

Polyoxygenated cembrane-type diterpenes from the Hainan soft coral Lobophytum crassum as a promising source of anticancer agents with ErbB3 and ROR1 inhibitory potential.

A detailed chemical investigation of the Hainan soft coral Lobophytum crassum led to the identification of a class of polyoxygenated cembrane-type macrocyclic diterpenes (1-28), including three new flexible cembranoids, lobophycrasins E-G (2-4), and twenty-five known analogues. Their structures were elucidated by combining extensive spectroscopic data analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) methods, the modified Mosher's method, X-ray diffraction analysis, and comparison with data reported in the literature. Bioassays revealed that sixteen cembranoids inhibited the proliferation of H1975, MDA-MB231, A549, and H1299 cells. Among them, Compounds 10, 17, and 20 exhibited significant antiproliferative activities with IC50 values of 1.92-8.82 µM, which are very similar to that of the positive control doxorubicin. Molecular mechanistic studies showed that the antitumour activity of Compound 10 was closely related to regulation of the ROR1 and ErbB3 signalling pathways. This study may provide insight into the discovery and utilization of marine macrocyclic cembranoids as lead compounds for anticancer drugs.

Revisiting Unaddressed Safety Concerns Regarding Intense Pulsed Light Treatment: Past and Present Perspectives.

BACKGROUND: The light spectrum of intense pulsed light (IPL) comprises visible to near-infrared light. It has been widely employed in the field of aesthetics for approximately 30 years. However, several studies have demonstrated the appearance of various undesirable biomarkers on the skin after IPL irradiation, which remain elucidated. METHODS: We reviewed the evolving concepts and explored the potentially harmful effects of IPL that may have been neglected in the past. RESULTS: Increased levels of reactive oxidative stress, p53, p16, proliferating cell nuclear antigen, interleukin-6, C-reactive protein, and cleaved caspase 3 and decreased albumin levels in human or mouse skin have been observed after IPL treatment. Visible and infrared light can exert harmful and beneficial effects on human skin. CONCLUSION: If perform improperly, IPL treatment may lead to cellular senescence, photoaging, photocarcinogenesis, thermal aging, and inflammaging. Further studies are required to verify the significance of the changes in the relevant biomarkers. The selection of treatment candidates, optimal parameters, and standardized protocols for IPL therapy are necessary.

In Vitro Insights into the Role of 7,8-Epoxy-11-Sinulariolide Acetate Isolated from Soft Coral Sinularia siaesensis in the Potential Attenuation of Inflammation and Osteoclastogenesis.

The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is essential for the process of bone remodeling. Excessive osteoclast differentiation plays a pivotal role in the pathogenesis of bone diseases such as rheumatoid arthritis and osteoporosis. In the present study, we examined whether 7,8-epoxy-11-sinulariolide acetate (Esa), a marine natural product present in soft coral Sinularia siaesensis, attenuates inflammation and osteoclastogenesis in vitro. The results indicated that Esa significantly inhibited lipopolysaccharide (LPS)-induced inflammation model of RAW264.7 cells and suppressed receptor activator for nuclear factor-κB ligand (RANKL)-triggered osteoclastogenesis. Esa significantly down-regulated the protein expression of iNOS, COX-2, and TNF-α by inhibiting the NF-κB/MAPK/PI3K pathways and reducing the release of reactive oxygen species (ROS) in RAW264.7 macrophages. Besides, Esa treatment significantly inhibited osteoclast differentiation and suppressed the expression of osteoclast-specific markers such as NFATC1, MMP-9, and CTSK proteins. These findings suggest that Esa may be a potential agent for the maintenance of bone homeostasis associated with inflammation.

Changes in Levels of Serum Cytokines and Chemokines in Perforated Appendicitis in Children.

Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix. This study aimed to identify systemic biomarkers to predict pediatric appendicitis at various time points. The study group comprised pediatric patients with clinically suspected appendicitis between 2016 and 2019. Pre-surgical serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), intercellular cell-adhesion molecule-1 (ICAM-1), and endothelial selectin (E-selectin) levels were tested from day 1 to day 3 of the disease course. The biomarker values were analyzed and compared between children with normal appendices and appendicitis and those with perforated appendicitis (PA) and non-perforated appendicitis. Among 226 pediatric patients, 106 had non-perforated appendicitis, 102 had PA, and 18 had normal appendices. The levels of all serum proinflammatory biomarkers were elevated in children with acute appendicitis compared with those in children with normal appendices. In addition, the serum IL-6 and TNF-α levels in children with PA were significantly higher, with an elevation in TNF-α levels from days 1 and 2. In addition, serum IL-6 levels increased significantly from days 2 and 3 (both p < 0.05). Serum ICAM-1 and E-selectin levels were elevated in the PA group, with consistently elevated levels within the first three days of admission (all p < 0.05). These results indicate that increased serum levels of proinflammatory biomarkers including IL-6, TNF-α, ICAM-1, and E-selectin could be used as parameters in the prediction and early diagnosis of acute appendicitis, especially in children with PA.

Advancements in Allergen Immunotherapy for the Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects individuals of all age groups, manifesting as a spectrum of symptoms varying from mild to severe. Allergen immunotherapy (AIT) involves the administration of allergen extracts and has emerged as a potential treatment strategy for modifying immune responses. Its pathogenesis involves epidermal barrier dysfunction, microbiome imbalance, immune dysregulation, and environmental factors. Existing treatment strategies encompass topical steroids to systemic agents, while AIT is under investigation as a potential immune-modifying alternative. Several studies have shown reductions in the severity scoring of atopic dermatitis (SCORAD) scores, daily rescue medication use, and visual analog scale (VAS) scores following AIT. Biomarker changes include increased IgG4 levels and decreased eosinophil counts. This review provides valuable insights for future research and clinical practice, exploring AIT as a viable option for the management of AD.

Augmented Reality in Spine Surgery: A Case Study of Atlantoaxial Instrumentation in Os Odontoideum.

Despite advancement in surgical innovation, C1-C2 fixation remains challenging due to risks of screw malposition and vertebral artery (VA) injuries. Traditional image-based navigation, while useful, often demands that surgeons frequently shift their attention to external monitors, potentially causing distractions. In this article, we introduce a microscope-based augmented reality (AR) navigation system that projects both anatomical information and real-time navigation images directly onto the surgical field. In the present case report, we discuss a 37-year-old female who suffered from os odontoideum with C1-C2 subluxation. Employing AR-assisted navigation, the patient underwent the successful posterior instrumentation of C1-C2. The integrated AR system offers direct visualization, potentially minimizing surgical distractions. In our opinion, as AR technology advances, its adoption in surgical practices and education is anticipated to expand.

Dichotomic Role of Low-Concentration EGCG in the Oxaliplatin Sensitivity of Colorectal Cancer Cells.

Although epigallocatechin-3-gallate (EGCG) can potentiate chemotherapeutic drugs at high concentrations, its clinical translation is hampered by exceeding possible concentration thresholds. This study proposes a dichotomous use of low-concentration EGCG in chemotherapy. During the first cycle of combined treatment with oxaliplatin (OXA), low-concentration EGCG antagonized the cytotoxic effect of OXA on colorectal cancer (CRC) cells. However, when OXA was subsequently administered, the sensitivity of CRC cells markedly increased. Although low-concentration EGCG counteracted OXA, it reduced the OXA-induced secretion of vascular endothelial growth factor by tumor cells, thereby contributing to the increase in the sensitivity of tumor cells to the second round of OXA treatment. Therefore, low-concentration EGCG showed potential as a viable adjunct to modulate chemosensitivity in CRC.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.

Inhibition of monoamine oxidase B reduces atherosclerosis and fatty liver in mice.

Oxidative stress is vital for pathophysiology of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Monoamine oxidase (MAO) is an important source of oxidative stress in the vascular system and liver. However, the effect of MAO inhibition on atherosclerosis and NAFLD has not been explored. In the present study, MAO A and B expressions were increased in atherosclerotic plaques in human and apolipoprotein E (ApoE)-deficient mice. Inhibition of MAO B (by deprenyl), but not MAO A (by clorgyline), reduced the atheroma area in the thoracic aorta and aortic sinus in ApoE-deficient mice fed the cholesterol-enriched diet for 15 weeks. MAO B inhibition attenuated oxidative stress, expression of adhesion molecules, production of inflammatory cytokines, and macrophage infiltration in atherosclerotic plaques and decreased plasma triglyceride and low-density lipoprotein (LDL) cholesterol concentrations. MAO B inhibition had no therapeutic effect on restenosis in the femoral artery wire-induced injury model in C57BL/6 mice. In the NAFLD mouse model, MAO B inhibition reduced lipid droplet deposition in the liver and hepatic total cholesterol and triglyceride levels in C57BL/6 mice fed high-fat diets for 10 weeks. Key enzymes for triglyceride and cholesterol biosynthesis (fatty acid synthase and 3-hydroxy-3-methylglutaryl-CoA reductase, HMGCR) and inflammatory markers were inhibited, and cholesterol clearance was up-regulated (increased LDL receptor expression and reduced proprotein convertase subtilisin/kexin type 9, PCSK9, expression) by MAO B inhibition in the liver. These results were also demonstrated in the HepG2 liver cell model. Our data suggest that MAO B inhibition is a potential and novel treatment for atherosclerosis and NAFLD.

Exposure to bisphenol A associated with multiple health-related outcomes in humans: An umbrella review of systematic reviews with meta-analyses.

Bisphenol A (BPA), a toxic endocrine disruptor, is widely distributed in the environment, and the effects of BPA exposure on human health outcomes are a critical issue. The objective of this study was to perform an umbrella review of published meta-analyses investigating the associations between BPA exposure and human-related health outcomes. The relevant reports were searched from three electronic databases from inception to July 12, 2023 including PubMed, ScienceDirect, and Embase. The reports that were systematic reviews with meta-analyses investigating the associations between BPA exposure and human health outcomes were included in our review. A total of 14 reports were included in our review. Several human health outcomes related to exposure BPA were investigated including maternal prenatal health, infant health, allergic diseases, kidney disease, metabolic syndromes, polycystic ovary syndrome, earlier puberty, inflammation and immune responses, and thyroid function in neonates. Among these health outcomes, BPA exposure was associated with multiple human health outcomes including preterm birth, allergic diseases, kidney disease, polycystic ovarian syndrome, obesity, type 2 diabetes, cardiovascular disease, hypertension, and inflammation and immune responses (C-reactive protein and interleukin-6). These results showed that BPA exposure has seriously affected human health. To protect human health, World Health Organization should develop meaningful regulations on BPA to decrease the environmental contamination.

Parental Postoperative Pain Management Perceptions, Attitudes, and Practices in Pediatric Limb Fractures.

BACKGROUND: Post-surgical pain in children is common, severe, and inadequately controlled. An effective model should involve the participation of parents. AIMS: To investigate parental perceptions, attitudes, and practices in postoperative pain management in children with limb fractures and analyze the factors affecting parental practices. DESIGN: This was a descriptive cross-sectional study. SETTINGS: Research was conducted at a tertiary Children's Hospital Affiliated with Soochow University. PARTICIPANTS: Parents whose children (age, 6-18 years) underwent orthopedic fracture surgery between January 1, 2020, and August 31, 2020, were recruited using purposive sampling. METHODS: The parents were asked to complete self-report questionnaires: "Pain Management Knowledge and Attitudes Questionnaire" and "Parents' Use of Pain Relief Strategies Questionnaire." The Wong-Baker Faces Scale was used to measure pain intensity in children. The Mann-Whitney U test, Kruskal-Wallis H test, and correlation and regression analyses were used for statistical analyses. RESULTS: Data of 180 parents were collected. Of the participants, 80.6%, 78.3%, and 71.7% had low-to-moderate scores for knowledge, general attitudes, and use of pain relief strategies, respectively. Moreover, 93.9% of parents had moderate-to-high scores for negative attitudes toward medication, despite 89.5% of them reporting moderate-to-high pain intensities in their children (median proxy-report of pain intensity, 7.0 [3.00]). Multivariate linear stepwise regression showed that parents' use of pain-relief strategies was related to their general attitudes, knowledge, and sex. CONCLUSIONS: Most parents had low-to-moderate scores for perceptions and general attitudes toward children's postoperative pain management, and use of pain relief strategies. Moreover, they lacked knowledge of and had negative attitudes toward pain assessment and analgesics, which significantly impacted their practices. CLINICAL IMPLICATIONS: Clinical pediatric nurses should provide appropriate support for the entire family of the child. Moreover, to enhance parental practices, they should develop targeted parental education programs for pain management, particularly regarding pain assessment tools and pain medications.

A Modified Suture Technique to Improve Scar Appearance in Wounds Under High Tension.

ABSTRACT: The purpose of this study was to introduce a modified suture technique and to compare its effects on skin scar formation with 2 traditional suture methods: simple interrupted suture (SIS) and vertical mattress suture (VMS). Three groups of healthy adult female Sprague-Dawley rats were selected (6 replicates in each group), and the full-thickness skin of 5 cm × 0.2 cm was cut off on the back of the rats after anesthesia. The wounds were then sutured using 1 of the 3 methods for each group: SIS, VMS, and a newly introduced modified vertical mattress suture (M-VMS) technique with the needle reinsertion at the exit point. A traction device was installed on the back of the rats to achieve high tension wounds. The tensile distance was increased by 1 mm every day for 20 days. After 20 days of healing, the hematoxylin-eosin staining method was used for observation of scar morphology. The collagen production rate was measured by Masson staining, and the type I collagen and type III collagen were detected by the immunofluorescence method. Immunohistochemical staining was used to detect the expression of myofibroblast marker α-smooth muscle actin, and real-time quantitative polymerase chain reaction and Western blot techniques were used to detect the expressions of transforming growth factors TGFß1, TGFß2, and TGFß3 to understand the mechanisms of scar formation. Results showed that the quantity and density of collagen fibers were both lower in the M-VMS group than in the other 2 groups. Immunofluorescence results showed that type I collagen was significantly lower, whereas type III collagen was significantly higher in the M-VMS group than in the other 2 groups. The expressions of α-smooth muscle actin and TGFß1 both were lower in the M-VMS group than in the other 2 groups. The expression of TGFß2 and TGFß3 had no obvious difference among the 3 groups. For wounds under high tension, compared with SIS and VMS methods, the M-VMS technique we proposed can reduce scar formation due to the reduction of collagen formation, myofibroblast expression, and TGFß1 expression.

Impact of post-implantation time on bioresorbable vascular scaffold outcomes for type C versus non-type C coronary lesions: A longer-term study.

BACKGROUND: We have demonstrated that bioresorbable vascular scaffold (BVS) for ACC/AHA type C lesions was associated with higher risks of long-term target lesion revascularization (TLR) and target lesion failure (TLF). We determined the specific time after which higher risks of BVS for type C lesions are reduced in a longer-term follow-up. METHODS: We analyzed data of 457 patients (59 ± 12 years, 87% male) with 714 BVS implanted for 529 lesions and a median follow-up of 56.4 (48.6-62.6) months. Patients with BVS for at least one type C lesion (N = 177) at index intervention and all non-type C lesions (N = 280) were compared for TLF (cardiac death, target vessel myocardial infarction, TLR). We specified the interactions between the non-type C versus type C group and the event-free survival times dichotomized at 24, 30, 32, 33, 36, and 39 months respectively. RESULTS: The type C group had more multivessel disease (86% versus 65%, p < 0.001), left anterior descending artery treated (68% versus 53%, p = 0.002), intravascular imaging used (48% vs. 25%, p < 0.001), and BVS (2.3 ± 0.9 vs. 1.1 ± 0.3, p < 0.001) implanted with a longer total length (57 ± 21 vs. 29 ± 8 mm, p < 0.001). The TLR or TLF was higher (both log-rank p < 0.05) in the type C than in the non-type C group. However, the risks of TLR (hazard ratio: 3.6, 95% CI = 1.1-11.6) and TLF (hazard ratio: 3.8, 95% CI = 1.2-12.1) for type C lesions only remained higher until 24 months post-BVS implantation. CONCLUSION: BVS provides a longer-term advantage, particularly for type C lesions with the majority requiring long stenting.

Stem Cell Therapy in Children with Traumatic Brain Injury.

Pediatric traumatic brain injury is a cause of major mortality, and resultant neurological sequelae areassociated with long-term morbidity. Increasing studies have revealed stem cell therapy to be a potential new treatment. However, much work is still required to clarify the mechanism of action of effective stem cell therapy, type of stem cell therapy, optimal timing of therapy initiation, combination of cocurrent medical treatment and patient selection criteria. This paper will focus on stem cell therapy in children with traumatic brain injury.

Mesenchymal Stem Cells in the Treatment of COVID-19.

Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond the respiratory system, affecting various organs and functions. In severe cases, it can progress to acute respiratory distress syndrome (ARDS) and multi-organ failure, often fueled by an excessive immune response known as a cytokine storm. Mesenchymal stem cells (MSCs) have considerable potential because they can mitigate inflammation, modulate immune responses, and promote tissue regeneration. Accumulating evidence underscores the efficacy and safety of MSCs in treating severe COVID-19 and ARDS. Nonetheless, critical aspects, such as optimal routes of MSC administration, appropriate dosage, treatment intervals, management of extrapulmonary complications, and potential pediatric applications, warrant further exploration. These research avenues hold promise for enriching our understanding and refining the application of MSCs in confronting the multifaceted challenges posed by COVID-19.