A novel hsa_circ_0006903 circular RNA promotes tumor development and dendritic cells activated expression in infantile hemangioma.

Background: Increasing reports revealed that circular RNAs (circRNAs) and immune cells infiltration were related with tumor development. However, its role in infantile hemangioma (IH) is unknown. We will explore a novel hsa_circ_0006903-based ceRNA network and investigate the landscape of dendritic cells activated expression in IH. Material and methods: Differentially expressed circRNAs (DECs) were identified from Gene Expression Omnibus (GEO) database. Regulatory networks and functional enrichment analysis were constructed. CIBERSORT was used to characterize immune cells composition. qRT-PCR was performed to detect the expression of hsa_circ_0006903 in cell lines. Then, the role of hsa_circ_0006903 in IH were validated in vitro using transwell assay. Immunofluorescence was applied to the colocalization of CD11b for dendritic cells activated as a biomarker in IH tissues. Results: Using GEO database, a total of 67 DECs were screened out in IH. Hsa_circ_0006903 was the most significant DECs. Then, a novel hsa_circ_0006903 circular RNA-ceRNA network was constructed. Mechanistically, functional enrichment analysis showed that the p53 signaling pathway played the most important roles, and hsa_circ_0006903/miR-6721-5p/CACNA2D2 and hsa_circ_0006903/miR-4786-3p/ATP13A4 axis were identified. CACNA2D2, ATP13A4, and P53 were significantly downregulated in IH cell lines. We validated that dendritic cell activated was significantly overexpressed. Moreover, CD11b as a biomarker of dendritic cells activated were tested in IH tissues. Finally, hsa_circ_0006903 was significantly overexpressed, and hsa_circ_0006903 promoted infantile hemangioma cell proliferation, invasion, and migration in vitro. Conclusion: Overall, our study revealed that a novel hsa_circ_0006903 promoted tumor progression, and indicated a potential biomarker CD11b of dendritic cells activated in IH.

The association of a frailty index derived from laboratory tests and vital signs with clinical outcomes in critical care patients with septic shock: a retrospective study based on the MIMIC-IV database.

PURPOSE: Frailty is a vulnerable state to stressors due to the loss of physiological reserve as a result of multisystem dysfunction. The physiological and laboratory-based frailty index (FI-Lab), depending on laboratory values and vital signs, is a powerful tool to capture frailty status. The aim of this study was to assess the relationship between FI-Lab and in-hospital mortality in patients with septic shock. METHODS: Baseline data for patients with sepsis in the intensive care unit were retrieved from the Critical Care Medicine Database (MIMIC-IV, v2.2). The primary outcome was mortality during hospitalization. The propensity score matching (PSM) method was used to analyze the basic conditions during hospitalization between groups.The FI-Lab was analysed for its relationship with in-hospital mortality using logistic regression according to continuous and categorical variables, respectively, and described using the restricted cubic spline (RCS). Survival was compared between groups using Kaplan-Meier (KM) curves. Subgroup analyses were used to improve the stability of the results. RESULTS: A total of 9219 patients were included. A cohort score of 1803 matched patients was generated after PSM. The analyses showed that non-surviving patients with septic shock in the ICU had a high FI-Lab index (P<0.001). FI-Lab, whether used as a continuous or categorical variable, increased with increasing FI-Lab and increased in-hospital mortality (P<0.001).Subgroup analyses showed similar results. RCS depicts this non-linear relationship. KM analysis shows the cumulative survival time during hospitalisation was significantly lower as FI-Lab increased (log-rank test, P<0.001). CONCLUSION: Elevated FI-Lab is associated with increased in-hospital mortality in patients with septic shock.

IRE1α Mediates the Hypertrophic Growth of Cardiomyocytes Through Facilitating the Formation of Initiation Complex to Promote the Translation of TOP-Motif Transcripts.

BACKGROUND: Cardiomyocyte growth is coupled with active protein synthesis, which is one of the basic biological processes in living cells. However, it is unclear whether the unfolded protein response transducers and effectors directly take part in the control of protein synthesis. The connection between critical functions of the unfolded protein response in cellular physiology and requirements of multiple processes for cell growth prompted us to investigate the role of the unfolded protein response in cell growth and underlying molecular mechanisms. METHODS: Cardiomyocyte-specific inositol-requiring enzyme 1α (IRE1α) knockout and overexpression mouse models were generated to explore its function in vivo. Neonatal rat ventricular myocytes were isolated and cultured to evaluate the role of IRE1α in cardiomyocyte growth in vitro. Mass spectrometry was conducted to identify novel interacting proteins of IRE1α. Ribosome sequencing and polysome profiling were performed to determine the molecular basis for the function of IRE1α in translational control. RESULTS: We show that IRE1α is required for cell growth in neonatal rat ventricular myocytes under prohypertrophy treatment and in HEK293 cells in response to serum stimulation. At the molecular level, IRE1α directly interacts with eIF4G and eIF3, 2 critical components of the translation initiation complex. We demonstrate that IRE1α facilitates the formation of the translation initiation complex around the endoplasmic reticulum and preferentially initiates the translation of transcripts with 5' terminal oligopyrimidine motifs. We then reveal that IRE1α plays an important role in determining the selectivity and translation of these transcripts. We next show that IRE1α stimulates the translation of epidermal growth factor receptor through an unannotated terminal oligopyrimidine motif in its 5' untranslated region. We further demonstrate a physiological role of IRE1α-governed protein translation by showing that IRE1α is essential for cardiomyocyte growth and cardiac functional maintenance under hemodynamic stress in vivo. CONCLUSIONS: These studies suggest a noncanonical, essential role of IRE1α in orchestrating protein synthesis, which may have important implications in cardiac hypertrophy in response to pressure overload and general cell growth under other physiological and pathological conditions.

Evaluation of linear dermatoses by reflectance confocal microscopy in children.

Lichen striatus (LS), linear psoriasis (LPs), linear cutaneous lupus erythematosus (LCLE) and linear lichen planus (LLP) often have similar clinical manifestations, which makes clinical diagnosis with the naked eye difficult; therefore, they are easily misdiagnosed. The purpose of this study was to determine whether reflectance confocal microscopy (RCM) is helpful in differentiating between these four linear dermatoses in children. This retrospective study included 14 patients with LS, nine with LPs, eight with LCLE and 12 with LLP. All patients were analysed using RCM, and biopsies were collected from lesions previously imaged by RCM. For LS, the dermal papillary rings were partially absent, but when present, manifested with small, homogeneously round, bright cells and occasionally highly refractive plump cellular structures, aggregated in clusters. LPs exhibited dark cyst-like structures with small, bright, round cells aggregated at the epidermal level; at the dermal-epidermal junction, homogeneously distributed, enlarged, faint dermal papillary rings and numerous enlarged low-refractive canalicular structures were observed in the superficial dermis. LCLE and LLP exhibited similar manifestations, including epidermal disarray, almost total absence of dermal papillary rings, and various sized refractive structures densely distributed in the dermis. The key distinguishing features of LCLE were the different sized structures mainly clustered around hair follicles, while LLP demonstrated dense structures with a scattered distribution. RCM may be used to distinguish between the key features of LS, LPs, LCLE and LLP in children.

Preliminary Evaluation of in vivo Reflectance Confocal Microscopy Features of Neonatal Lupus Erythematosus.

INTRODUCTION: Neonatal lupus erythematosus (NLE) is a rare autoimmune disease, which needs to be distinguished from eczema, congenital syphilis, and tinea corporis in newborns. Reflectance confocal microscopy (RCM) could be a helpful noninvasive diagnostic tool, which has been used to evaluate several inflammatory skin conditions. The aim of this study was to describe the RCM characteristics of NLE. METHODS: Eleven NLE patients were included in the study, and all patients were evaluated clinically with RCM. We also evaluated RCM images from 11 eczema patients as controls. RESULTS: Some major key diagnostic features of NLE can be observed by RCM: an enlarged honeycomb pattern (9/11, 81.8%), round-to-oval cyst-like structures were present (6/11, 54.5%), the normal ring-like structures were totally or partially obliterated (11/11, 100%) at the level of the dermo-epidermal junction, medium refractivity collagen fibers that were disorganized (10/11, 90.9%), numerous high refractivity round cells (11/11, 100%) in the dermis. CONCLUSION: RCM allows the visualization of major key diagnostic features of NLE and serves as a complementary diagnostic tool for NLE.

Reflectance confocal microscopy as a complementary diagnostic tool for greyish-brown dermatoses in children.

Mastocytosis, lichen planus pigmentosus (LPP), fixed drug eruption (FDE) and café-au-lait macules (CALM) have a similar appearance, often lead to misdiagnosis and missed diagnoses. At the outpatient clinic at Tianjin Children's Hospital in 21 patients with mastocytosis, 18 with LPP, 11 with FDE and 12 with CALM we evaluated the characteristics and distinguishing features of their dermatoses using reflectance confocal microscopy (RCM). In mastocytosis, the dermal papillary rings generally had a significantly increased bright refractive index and the superficial dermis was filled with moderate refractive flocculent material. In LPP, the dermal papillary rings were absent and numerous different-sized cellular structures were densely distributed in the superficial dermis. In FDE, the dermal papillary rings were intact with a significantly increased bright refractive index. In CALM, normal dermal papillary rings were detected with a uniformly slightly increased refractive index and no obvious abnormality in the superficial dermis. RCM allows for real-time visualization of the major key diagnostic and distinguishing features of four greyish-brown dermatoses in children.

Linear alopecia in pediatrics: RCM and dermoscopy reveal diagnostic cues.

BACKGROUND: Alopecia areata (AA), trichotillomania (TM), nevus sebaceous (NS), and linear scleroderma en coup de sabre (LSCS) can all present with a patch of linear alopecia, making diagnosis challenging. The purpose of this study was to combine reflectance confocal microscopy (RCM) and dermoscopy in the diagnosis of these lesions in children. METHODS: A total of 36 patients with linear alopecia were enrolled, of whom 14 had AA, seven had TM, nine had NS, and six had LSCS. We evaluated the characteristics and distinguishing features of the four conditions using RCM and dermoscopy. RESULTS: The key to differential diagnosis was the dermal Hair follicle density in the dermis was decreased in AA, and the size and density of the follicular openings were normal in TM. In NS, the major features were petal-like and frogspawn-like structures. In LSCS, dermal papillary rings, sebaceous glands, and follicles were partially or completely missing, and abundant fibrous material was distributed in the dermis. Dermoscopy revealed alopecia, and all four conditions resulted in decreased hair density. AA patients exhibited yellow dots, black dots, and exclamation mark hairs. TM patients presented with irregularly broken hairs and blood spots. Both NS and LSCS patients exhibited an absence of follicular openings; NS patients demonstrated whitish and yellowish round structures, while an atrophic area with white patches, linear vessels, and no yellow or black dots was observed in LSCS patients CONCLUSION: RCM combined with dermoscopy can provide additional information on disease states and differentiate between AA, TM, NS, and LSCS.

Dermoscopic and reflectance confocal microscopic features of children scabies.

OBJECTIVE: To summarize the image features of dermatoscopy and reflectance confocal microscopy (RCM) in children with scabies, and to explore the clinical significance in the diagnosis of children scabies. METHODS: A retrospective analysis was conducted on 102 children scabies diagnosed clinically in the dermatology outpatient department of Tianjin Children's Hospital from April 2018 to June 2022. All children were examined by dermatoscopy and RCM, and images were collected. RESULTS: 102 patients, 92 patients (90.2%) showed characteristic dermoscopic manifestations: white tunnels and small brown or dark brown triangular structures at their ends. 91 patients (89.2%) showed characteristic reflectance confocal microscopic manifestations: tunnels, scabies mites, feces, and eggs in the epidermal layer. All patients showed different degrees of non-specific manifestations of dermoscopy and RCM. CONCLUSION: Children scabies have typical dermatoscopic and reflectance confocal microscopic characteristics, and dermatoscopy and RCM are effective non-invasive diagnostic methods with high clinical application value in the diagnosis and differential diagnosis of children scabies.

An improved blood hemorrhaging treatment using diatoms frustules, by alternating Ca and light levels in cultures.

Hemorrhage control requires hemostatic materials that are both effective and biocompatible. Among these, diatom biosilica (DBs) could significantly improve hemorrhage control, but it induces hemolysis (the hemolysis rate > 5%). Thus, the purpose of this study was to explore the influence of Ca2+ biomineralization on DBs for developing fast hemostatic materials with a low hemolysis rate. Here, CaCl2 was added to the diatom medium under high light (cool white, fluorescent lamps, 67.5 µmol m-2 s-1), producing Ca-DBs-3 with a particle size of 40-50 µm and a Ca2+ content of Ca-DBs-3 obtained from the higher concentration CaCl2 group (6.7 mmol L-1) of 0.16%. The liquid absorption capacity of Ca-DBs-3 was 30.43 ± 0.57 times its dry weight; the in vitro clotting time was comparable to QuikClot® zeolite; the hemostatic time and blood loss using the rat tail amputation model were 36.40 ± 2.52 s and 0.39 ± 0.12 g, which were 40.72% and 19.50% of QuikClot® zeolite, respectively. Ca-DBs-3 showed no apparent toxicity to L929 cells (cell viability > 80%) and was non-hemolysis (the hemolysis rate < 2%). This study prepared Ca-DBs-3 with a rapid hemostatic effect and good biocompatibility, providing a path to develop diatom biosilica hemostatic materials. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00180-3.

Reflectance confocal microscopy features of vulvar lichen sclerosus in Chinese juvenile girls.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis of unknown pathogenesis, characterized by porcelain-white atrophic plaques around the vulvar and anal areas in girls. With this communication, we performed the study on 16 female girls with clinically and histologically confirmed VLS, described the main identifying characteristics of the lesions in reflectance confocal microscopy (RCM) and elucidated the corresponding relationship between RCM findings and histology. We recommend RCM, a noninvasive technique, as a complementary diagnostic tool for VLS.

Preliminary evaluation of penile papule dermatoses with reflectance confocal microscopy in children.

BACKGROUND: Owing to their similar appearance, lichen striatus (LS), lichen nitidus (LN), juvenile xanthogranuloma (JXG), and molluscum contagiosum (MC) on the penis often lead to misdiagnosis and missed diagnosis, especially in children. In vivo evaluation of penile dermatoses with reflectance confocal microscopy (RCM) is helpful in the diagnosis of these ambiguous lesions in children. METHODS: We recruited 12 patients with LS, nine with LN, seven with JXG, and nine with MC and evaluated the characteristics and distinguishing features of the four kinds of papule dermatoses on the penis using RCM. RESULTS: The four dermatoses all had unique RCM features. LS generally showed focally destroyed dermal papillary rings, with numerous mononuclear cell clusters aggregated inside the papillary rings, and highly refractive clumps were observed. For LN, the dermal papillary rings were completely destroyed and arranged in a solitary, enlarged, cavity-like structure, in which round cells, particulate matter structures, and plump cellular structures were aggregated; the adjacent skin was completely normal. In JXG, the dermal papillary rings were significantly dilated, and the superficial dermis was filled with different-sized large bright ring cells; smaller, refractive, roundish structures; and particulate matter. For MC, the normal structures completely disappeared; the lesions were arranged in a crater-shaped structure; and a mass-like substance formed by the aggregation of multiple, uniform, roundish structures was observed within the crater. CONCLUSION: RCM allows for real-time visualization of major key diagnostic and distinguishing features of four papule dermatoses, LS, LN, JXG, and MC, on the penis in children.

Reflectance confocal microscopy-assisted diagnosis of lichen planus pigmentosus distributed along multiple unilateral Blaschko's lines in a child: A case report.

A boy with a 2-year history of asymptomatic, linear pigmented macules involving the right side of the trunk and right upper limb. RCM revealed the dermal papillary rings were destroyed, and numerous irregular particulate structures with high refractive values were distributed in the superficial dermis. The RCM features implied the possibility of interface dermatitis. RCM was a complementary diagnostic tool for linear pigmented macules.

In vivo evaluation of vulvar lichen sclerosus with reflectance confocal microscopy and therapeutic monitoring in children.

BACKGROUND: Vulvar lichen sclerosus (VLS) in girls presents with itching, dysuria, and constipation and may result in the loss of vulvar architecture. In patients with an ambiguous clinical presentation, reflectance confocal microscopy (RCM) could be a helpful noninvasive diagnostic tool. The aim of this study was to describe the RCM characteristics of VLS and explore the clinical application value of RCM in therapeutic monitoring. METHODS: Sixteen patients with VLS were included in the study. All patients were periodically evaluated clinically with RCM, and different treatment regimens were given based on the patient's clinical appearances and RCM features. RESULTS: Some major key diagnostic features of VLS can be observed by RCM, including round to oval cyst-like structures with medium-to-low-refractive keratinoid substances (75%), thinning of the epidermal thickness (100%), destruction of the ring-like structures around dermal papillae (100%), disorderly distributed coarse medium-refractive fibrous material (100%),polygonal, plump, high-refractive cellular structures and linear low-refractive canalicular structures (100%). All of these characteristics had a high correspondence with histopathological features. The clinical manifestations improved after individualized treatment regimens based on the clinical appearances and RCM features. CONCLUSION: RCM allows the visualization of major key diagnostic features of VLS and represents a valid option for objective therapeutic monitoring.

Optimal Superpixel Kernel-Based Kernel Low-Rank and Sparsity Representation for Brain Tumour Segmentation.

Given the need for quantitative measurement and 3D visualisation of brain tumours, more and more attention has been paid to the automatic segmentation of tumour regions from brain tumour magnetic resonance (MR) images. In view of the uneven grey distribution of MR images and the fuzzy boundaries of brain tumours, a representation model based on the joint constraints of kernel low-rank and sparsity (KLRR-SR) is proposed to mine the characteristics and structural prior knowledge of brain tumour image in the spectral kernel space. In addition, the optimal kernel based on superpixel uniform regions and multikernel learning (MKL) is constructed to improve the accuracy of the pairwise similarity measurement of pixels in the kernel space. By introducing the optimal kernel into KLRR-SR, the coefficient matrix can be solved, which allows brain tumour segmentation results to conform with the spatial information of the image. The experimental results demonstrate that the segmentation accuracy of the proposed method is superior to several existing methods under different indicators and that the sparsity constraint for the coefficient matrix in the kernel space, which is integrated into the kernel low-rank model, has certain effects in preserving the local structure and details of brain tumours.