A bibliometric study: Relevant studies on scar laser therapy since the 21st century.

To summarise research studies on scar laser therapy since the 21st century using bibliometric methods, and to speculate on the possible development in the future. The literature about scar laser therapy in Web of Science database was searched. CiteSpace and VOSviewer were used to analyse main countries, institutions, journals，subject hotspots and trends, etc. A total of 884 papers have been published since the 21st century. These publications were written by 653 authors from 515 institutions in 58 countries. The United States published 287 papers in this field and ranks first. Laser in Surgery and Medicine is the most widely published journal, with Shumaker as the core author. The main keyword clustering includes terms such as combination therapy, wound healing, fractional photothermolysis, experience, scar formation, etc. CiteSpace and VOSviewer were used to sort out and summarise the countries, institutions, authors, journals, research hotspots and frontier topics of related literature about scar laser therapy since the 21st century. The current situation of its application and basic scientific research in clinical treatments were summarised briefly. This provides a new idea for the development and research of scar laser therapy in the future.

Preoperative MRI Evaluation of Hand Vessels in Children With Congenital Syndactyly Malformation by a Contrast-Enhanced Three-Dimensional Water-Selective Cartilage Scan.

Background: It is crucial to preoperatively assess the arteries of the hands in congenital syndactyly malformation (CSM) patients because this information can affect the therapeutic outcome and prognosis. Objective: To investigate the value of a contrast-enhanced three-dimensional water-selective cartilage scan for the preoperative evaluation of CSM in children. Materials and Methods: Contrast-enhanced three-dimensional water-selective cartilage scan 3.0 T magnetic resonance imaging (MRI) performed in 16 clinically diagnosed CSM patients with 17 affected hands. The arteries of the hands were displayed with a focus on the bifurcation position of the common palmar digital arteries (CPDAs) and the maturity of the proper palmar digital arteries (PPDAs). The MRI results were interpreted by consensus between two experienced pediatric radiologists with 10 years of MRI experience each. The MRI findings were compared with the operation results. Results: Of 51 CPDAs in the 17 affected hands, MRI showed that 30 had an abnormal bifurcation position and 20 had a normal position, and of the 102 PPDAs, 14 were shown to have an abnormal maturity and 85 a normal state, which were confirmed by surgery. The accuracy, sensitivity and specificity for determining the bifurcation position of the CPDAs based on MR maximum intensity projection reconstructed images were 98.04% (50/51), 96.77% (30/31) and 100% (20/20), respectively. The maturity of the PPDAs was judged by MR maximum intensity projection reconstructed images with an accuracy, sensitivity and specificity of 97.06% (99/102), 82.35% (14/17) and 100% (85/85), respectively. Conclusion: Contrast-enhanced three-dimensional water-selective cartilage scan has excellent performance in displaying the bifurcation position of the CPDAs and the maturity of the PPDAs and is of high value for the preoperative evaluation of CSM in children.

HOTAIR/Sp1/miR-199a critically regulates cancer stemness and malignant progression of cutaneous squamous cell carcinoma.

The long non-coding RNA (lncRNA), HOX antisense intergenic RNA (HOTAIR) is a well-characterized oncogene in multiple human cancers, but not in cutaneous squamous cell carcinoma (CSCC). In this study, we focused on investigating the potential role of HOTAIR in stemness of CSCC. By measuring its expression using RT-qPCR in CSCC vs. normal tissues, as well as in CSCC cell lines A431 or SCC13, A431- or SCC13-derived CSCC stem cells (CSCSCs), and normal skin fibroblasts (HSFs), we detected higher expression of HOTAIR in CSCC than in normal tissues, in recurrent than in non-recurrent CSCC tissues, in CSCCs and CSCSCs than in HSFs, and particularly, in CSCSCs than in CSCCs. Kaplan-Meier analysis suggested that higher expression of HOTAIR was positively correlated with worse overall survival of CSCC patients. Functional assays on colony formation, EdU incorporation, sphere formation, western blot on stem-cell biomarkers, and in vivo models showed that HOTAIR was essential in maintaining multiple stem cell phenotypes of CSCSCs in vitro and in vivo xenograft growth as well as metastasis. Mechanistically, HOTAIR directly interacted with and up-regulated Sp1. Sp1 then induced DNMT1-mediated promoter methylation and direct transcriptional repression of miR-199a-5p. Targeting Sp1 or DNMT1 further boosted the in vivo anti-tumor and anti-metastasis activities of targeting HOTAIR. In conclusion, HOTAIR, by up-regulating Sp1 and targeting miR-199a, promotes stemness and progression of CSCC. Targeting HOTAIR, Sp1 or the underlying mechanisms may thus benefit CSCC treatment.

Application of multiple injections of contrast agent in head and neck CT arteriovenous angiography in children: Study protocol clinical trial (SPIRIT Compliant).

OBJECTIVE: To investigate the application value of multiple injections of contrast agent in head and neck CT arteriovenous angiography in children. METHODS: A total of 100 children aged 6 to 7 years who needed head and neck CT arteriovenous angiography were prospectively selected. They were randomly divided into a control group and a research group, with 50 children in each group. The same scanning parameters and reconstruction methods were used. The right median cubital vein was injected intravenously with the contrast agent Omnipaque (350 mg I/ml). For children in the control group, a bolus of undiluted contrast agent (dose was 2 ml/kg, upper limit was 50 ml) was injected 1 time. The arterial phase and vein phase of the head and neck vessels were scanned. For children in the research group, a contrast agent bolus diluted with saline to a concentration of 20% was first injected (dose was 1 ml/kg, upper limit was 25 ml), and then an undiluted contrast agent bolus (dose was 1 ml/kg, upper limit was 25 ml) was injected. Thresholds were used to trigger the scanning of the head and neck arterial phases. The CT image quality of the head and neck arteries and veins, radiation dose and contrast agent dose were compared between the 2 groups. RESULTS: Subjective evaluation of CT image quality of arteries: there were 47 cases of 4 points and 3 cases of 3 points in the control group and 34 cases of 4 points and 16 cases of 3 points in the research group. Subjective evaluation of CT image quality of veins: there were 47 cases of 4 points and 3 cases of 3 points in the control group and 5 cases of 4 points, 42 cases of 3 points and 3 cases of 2 points in the research group. The CT value of brain arterial vessel enhancement was higher in the control group than the research group, and the difference was statistically significant (P < .05). The CT value of vein enhancement was higher in the control group than the research group, and the difference was statistically significant (P < .05). The X-ray dose in the research group was 51% lower than that in the control group; the contrast agent dose in the research group was 44% lower than that in the control group. CONCLUSION: For the head and neck enhanced CT examination of children, the method of first bolus injection of 20% diluted contrast agent and later bolus injection of undiluted contrast agent can clearly demonstrate the head and neck arteries and veins one time, reducing the X-ray dose and contrast agent dose, which has clinical practical value in the enhanced CT examination of children with head and neck disease.

Sorafenib sensitizes melanoma cells to vemurafenib through ferroptosis.

BACKGROUND: BRAF gene mutation causes melanoma patients to develop drug resistance after 8-9 months BRAF inhibitors treatment. Therefore, overcoming BRAF inhibitor resistance has important implications for improving patient survival. Sorafenib directly inhibits tumor cell proliferation by blocking the RAF/MEK/ERK-mediated cell signaling pathway. It remains unknown that whether the combination of sorafenib with vemurafenib could sensitize melanoma cells to vemurafenib, and the underlying mechanism needs to be clarified. METHODS: Vemurafenib resistant melanoma cells A375/Vem and SK-Mel-28/Vem were established by exposing to a series of concentration of vemurafenib. Cell viability was measured when A375 and SK-Mel-28 cells treated with vemurafenib or combined with sorafenib. Meanwhile the levels of Iron, GSH, MDA and reactive oxygen species (ROS) were detected. Finally we examined that whether sorafenib sensitizes melanoma cells to vemurafenib through ferroptosis. RESULTS: We found that sorafenib sensitized melanoma cells to vemurafenib. Sorafenib treatment did not significantly alter the production of ROS and the content of iron, GSH and MDA in vemurafenib resistant cells, but cotreatment of sorafenib and vemurafenib dramatically upregulated ROS production, MDA and iron, but decreased GSH concentration. Interestingly, sorafenib strongly promoted vemurafenib-induced cell death, which was blocked by lipid peroxidation inhibitors ferrostatin-1 but not ZVAD-FMK or necrosulfonamid. CONCLUSIONS: Sorafenib sensitized melanoma cells to vemurafenib by increasing ROS production through ferroptosis. Our study reveals that the combination of sorafenib may provide a novel strategy of vemurafenib resistant melanoma therapy.

Over Expressed TKTL1, CIP-2A, and B-MYB Proteins in Uterine Cervix Epithelium Scrapings as Potential Risk Predictive Biomarkers in HR-HPV-Infected LSIL/ASCUS Patients.

High oncogenic risk human papillomaviruses (HR-HPVs) promote cervical carcinoma development, the fourth most common feminine cancer. A slow oncodevelopmental phase-defined histopathologically as Cervical Intraepithelial Neoplasia (CIN) grades 1-3, or cytologically as Low- or High-grade Squamous Intraepithelial Lesions (LSIL or HSIL)-precedes the malignancy. Cervical carcinoma screenings through HR-HPV genotyping and Pap smears are regularly performed in Western countries. Faulty cytology screening or genotyping or patients' non-compliance with follow-ups can let slip an oncoprogression diagnosis. Novel biomarker tests flanking HR-HPV genotyping and cytology could objectively predict the risk of disease progression thus helping triage LSIL/ASCUS patients. Here, anonymized leftovers of fresh cervical epithelium scrapings from twice (LSIL/ASCUS and HR-HPV DNA)-positive and twice (Pap smear- and HR-HPV DNA)-negative (control) patients in a proteome-preserving solution served to assess the biomarker worth of three cervical carcinoma-related proteins, i.e., B-MYB (or MYBL2), Cancerous Inhibitor of PP2A (CIP-2a), and transketolase-like1 (TKTL1). Leftovers anonymity was strictly kept and storage at -80°C, protein extraction, immunoblotting, and band densitometry were blindly performed. Only after tests completion, the anonymous yet code-corresponding HR-HPV-genotyping and cytology data allowed to assign each sample to the twice-positive or twice-negative group. Descriptive statistics showed that the three proteins levels significantly increased in the twice-positive vs. twice-negative scrapings. Diagnostic ROC curve analysis identified each protein's Optimal Decision Threshold (OTD) showing that TKTL1 and CIP-2a are stronger risk predictive biomarkers (Sensitivity, 0.91-0.93; Specificity, 0.77-0.83) than B-MYB. Logistic Regression coupled with Likelihood-Ratio Tests confirmed that a highly significant relation links increasing TKTL1/CIP-2a/B-MYB protein levels in twice-positive cervical scrapings to the risk of HR-HPV-driven oncoprogression. Finally, a 3 year clinical follow-up showed that 13 patients (50% of total) of the twice-positive group with biomarker values over OTDs compliantly underwent scheduled colposcopy and biopsy. Of these, 11 (i.e., 84.7%) received a positive histological diagnosis, i.e., CIN1 (n = 5; 38.5%) or CIN2/CIN2+ (n = 6; 46,2%). Therefore, TKTL1/CIP-2a/B-MYB protein levels could objectively predict oncoprogression risk in twice (HR-HPV- and Pap smear)-positive women. Further studies will assess the translatability of these findings into clinical settings.

Calcium-Sensing Receptor Antagonist NPS 2143 Restores Amyloid Precursor Protein Physiological Non-Amyloidogenic Processing in Aß-Exposed Adult Human Astrocytes.

Physiological non-amyloidogenic processing (NAP) of amyloid precursor holoprotein (hAPP) by α-secretases (e.g., ADAM10) extracellularly sheds neurotrophic/neuroprotective soluble (s)APPα and precludes amyloid-ß peptides (Aßs) production via ß-secretase amyloidogenic processing (AP). Evidence exists that Aßs interact with calcium-sensing receptors (CaSRs) in human astrocytes and neurons, driving the overrelease of toxic Aß42/Aß42-os (oligomers), which is completely blocked by CaSR antagonist (calcilytic) NPS 2143. Here, we investigated the mechanisms underlying NPS 2143 beneficial effects in human astrocytes. Moreover, because Alzheimer's disease (AD) involves neuroinflammation, we examined whether NPS 2143 remained beneficial when both fibrillary (f)Aß25-35 and a microglial cytokine mixture (CMT) were present. Thus, hAPP NAP prevailed over AP in untreated astrocytes, which extracellularly shed all synthesized sAPPα while secreting basal Aß40/42 amounts. Conversely, fAß25-35 alone dramatically reduced sAPPα extracellular shedding while driving Aß42/Aß42-os oversecretion that CMT accelerated but not increased, despite a concurring hAPP overexpression. NPS 2143 promoted hAPP and ADAM10 translocation to the plasma membrane, thereby restoring sAPPα extracellular shedding and fully suppressing any Aß42/Aß42-os oversecretion, but left hAPP expression unaffected. Therefore, as anti-AD therapeutics calcilytics support neuronal viability by safeguarding astrocytes neurotrophic/neuroprotective sAPPα shedding, suppressing neurons and astrocytes Aß42/Aß42-os build-up/secretion, and remaining effective even under AD-typical neuroinflammatory conditions.

Biocompatible Silk Noil-Based Three-Dimensional Carded-Needled Nonwoven Scaffolds Guide the Engineering of Novel Skin Connective Tissue.

Retracting hypertrophic scars resulting from healed burn wounds heavily impact on the patients' life quality. Biomaterial scaffolds guiding burned-out skin regeneration could suppress or lessen scar retraction. Here we report a novel silk noil-based three-dimensional (3D) nonwoven scaffold produced by carding and needling with no formic acid exposure, which might improve burn healing. Once wetted, it displays human skin-like physical features and a high biocompatibility. Human keratinocyte-like cervical carcinoma C4-I cells seeded onto the carded-needled nonwovens in vitro quickly adhered to them, grew, and actively metabolized glutamine releasing lactate. As on plastic, they released no proinflammatory IL-1ß, although secreting tumor necrosis factor-alpha, an inducer of the autocrine mitogen amphiregulin in such cells. Once grafted into interscapular subcutaneous tissue of mice, carded-needled nonwovens guided the afresh assembly of a connective tissue enveloping the fibroin microfibers and filling the interposed voids within 3 months. Fibroblasts and a few poly- or mononucleated macrophages populated the engineered tissue. Besides, its extracellular matrix contained thin sparse collagen fibrils and a newly formed vascular network whose endothelin-1-expressing endothelial cells grew first on the fibroin microfibrils and later expanded into the intervening matrix. Remarkably, no infiltrates of inflammatory leukocytes and no packed collagen fibers bundles among fibroin microfibers, no fibrous capsules at the grafts periphery, and hence no foreign body response was obtained at the end of 3 months of observation. Therefore, we posit that silk noil-based 3D carded-needled nonwoven scaffolds are tools for translational medicine studies as they could guide connective tissue regeneration at deep burn wounds averting scar retraction with good functional results.

Calcium-Sensing Receptors of Human Neural Cells Play Crucial Roles in Alzheimer's Disease.

In aged subjects, late-onset Alzheimer's disease (LOAD) starts in the lateral entorhinal allocortex where a failure of clearance mechanisms triggers an accumulation of neurotoxic amyloid-ß42 oligomers (Aß42-os). In neurons and astrocytes, Aß42-os enhance the transcription of Aß precursor protein (APP) and ß-secretase/BACE1 genes. Thus, by acting together with γ-secretase, the surpluses of APP and BACE1 amplify the endogenous production of Aß42-os which pile up, damage mitochondria, and are oversecreted. At the plasmalemma, exogenous Aß42-os bind neurons' and astrocytes' calcium-sensing receptors (CaSRs) activating a set of intracellular signaling pathways which upkeep Aß42-os intracellular accumulation and oversecretion by hindering Aß42-os proteolysis. In addition, Aß42-os accumulating in the extracellular milieu spread and reach mounting numbers of adjacent and remoter teams of neurons and astrocytes which in turn are recruited, again via Aß42-os•CaSR-governed mechanisms, to produce and release additional Aß42-os amounts. This relentless self-sustaining mechanism drives AD progression toward upper cortical areas. Later on accumulating Aß42-os elicit the advent of hyperphosphorylated (p)-Tau oligomers which acting together with Aß42-os and other glial neurotoxins cooperatively destroy wider and wider cognition-related cortical areas. In parallel, Aß42-os•CaSR signals also elicit an excess production and secretion of nitric oxide and vascular endothelial growth factor-A from astrocytes, of Aß42-os and myelin basic protein from oligodendrocytes, and of proinflammatory cytokines, nitric oxide and (likely) Aß42-os from microglia. Activated astrocytes and microglia survive the toxic onslaught, whereas neurons and oligodendrocytes increasingly die. However, we have shown that highly selective allosteric CaSR antagonists (calcilytics), like NPS 2143 and NPS 89626, efficiently suppress all the neurotoxic effects Aß42-os•CaSR signaling drives in cultured cortical untransformed human neurons and astrocytes. In fact, calcilytics increase Aß42 proteolysis and discontinue the oversecretion of Aß42-os, nitric oxide, and vascular endothelial growth factor-A from both astrocytes and neurons. Seemingly, calcilytics would also benefit the other types of glial cells and cerebrovascular cells otherwise damaged by the effects of Aß42-os•CaSR signaling. Thus, given at amnestic minor cognitive impairment (aMCI) or initial symptomatic stages, calcilytics could prevent or terminate the propagation of LOAD neuropathology and preserve human neurons' viability and hence patients' cognitive abilities.

Eukaryotic initiation factor 6 modulates myofibroblast differentiation at transforming growth factor-ß1 transcription level via H2A.Z occupancy and Sp1 recruitment.

Eukaryotic initiation factor 6 (eIF6) is a pivotal regulator of ribosomal function, participating in translational control. Previously our data suggested that eIF6 acts as a key binding protein of P311 (a hypertrophic scar-related protein; also known as NREP). However, a comprehensive investigation of its functional role and the underlying mechanisms in modulation of myofibroblast (a key effector of hypertrophic scar formation) differentiation remains unclear. Here, we identified that eIF6 is a novel regulator of transforming growth factor-ß1 (TGF-ß1) expression at transcription level, which plays a key role in myofibroblast differentiation. Mechanistically, this effect is associated with eIF6 altering the occupancy of the TGF-ß1 promoter by H2A.Z (Swiss-Prot P0C0S6) and Sp1. Accordingly, modulation of eIF6 expression in myofibroblasts significantly affects their differentiation via the TGF-ß/Smad signaling pathway, which was verified in vivo by the observation that heterozygote eIF6(+/-) mice exhibited enhanced TGF-ß1 production coupled with increased α-smooth muscle actin (α-SMA)(+) myofibroblasts after skin injury. Overall, our data reveal a novel transcriptional regulatory mechanism of eIF6 that acts on facilitating Sp1 recruitment to TGF-ß1 promoter via H2A.Z depletion and thus results in increased TGF-ß1 transcription, which contributes to myofibroblast differentiation.

Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCζ and caspase-3 at the nuclear envelope of etoposide-treated human cervical carcinoma C4-I cells.

Protein kinase (PK)Cζ signaling at various subcellular levels affects cell survival, differentiation, growth and/or apoptosis. However, the mechanisms modulating PKCζ activity at the nuclear membrane (NM) are not yet fully understood. Previously, we demonstrated that PKCζ interacts with the B­cell lymphoma 10 (Bcl10) protein at the NM of human cervical carcinoma (HCC) C4­I cells. In the present study, we aimed to further clarify the interactions between PKCζ, Bcl10 and other proteins co-immunoprecipitated from NMs isolated from untreated and etoposide (also known as VP­16; 2.0 µg/ml)­treated C4­I cells using biochemical and proteomics analyses. Aside from the Bcl10 protein, 3­phosphoinositide­dependent protein kinase­1 (PDK1) also co-immunoprecipitated with PKCζ from NMs of C4­I cells, indicating the assembly of a heterotrimeric complex, which increased with time in VP­16­exposed cells, as did the activity of PDK1­phosphorylated­PKCζ. In turn, PKCζ­phosphorylated­Bcl10 straddled an enlarged complex which comprised caspase­3. Subsequently, activity­enhanced caspase­3 cleaved and inactivated PKCζ. Finally, the suppression of Bcl10 using specific siRNA or lentiviral transduction prevented the increase in the PDK1•PKCζ association, the increase in the activity of PKCζ and caspase­3, as well as the caspase­3­mediated PKCζ proteolysis and inactivation from occurring at the NMs of the VP­16­exposed C4­I cells. Our observations provide evidence that Bcl10 acts as a pivotal pro-apoptotic protein which crucially nucleates complexes comprising PDK1, PKCζ and active caspase­3 at the NMs of VP­16­exposed C4­I cells. Hence, our data suggest that Bcl10 and PKCζ are potential therapeutic targets in the treatment of HCC.

Novel bilayer wound dressing composed of silicone rubber with particular micropores enhanced wound re-epithelialization and contraction.

Wound dressing is critical important for cutaneous wound healing. However, the application of current products is limited due to poor mechanical property, unsuitable water vapor transmission rate (WVTR), poor anti-infective property or poor biocompatibility, etc. In the present study, a microporous silicone rubber membrane bilayer (SRM-B) composed of two layers with different pore sizes was prepared. The physical properties, the influences of pore structure on the bacterial penetration, the cell adhesion and proliferation were studied. Lastly, the effects of the SRM-B on the healing of a mouse full-thickness wound were examined. The data showed that the small pore upper layer of SRM-B could effectively prevent the bacterial invasion, as well as properly keep the water vapor transmission rate; the large pore lower layer of SRM-B could promote the cell adhesion and proliferation. The in vivo results showed that SRM-B could significantly enhance wound re-epithelialization and contraction, which accelerated the wound healing. Our data suggested that the SRM-B, with different particular pore sizes, could serve as a kind of promising wound dressing.

Mitsugumin 53 protects the kidney from severe burn injury in mice.

Mitsugumin 53 (MG53), a newly identified muscle-specific protein, is an essential component of the cell membrane repair machinery in skeletal and cardiac muscle. However, the role of MG53 after burns in other tissues remains unclear. This study aims to investigate the possible roles of MG53 in the protection of the kidney after severe burn injury, and an animal scalding model of 30% of total body surface area (TBSA) was used. Recombinant human MG53 (rhMG53) or bovine serum albumin (BSA) was injected intravenously via the tail vein. Data showed that the mortality in the MG53-treated group was lower than that in control group. Administration of rhMG53 may alleviate histological alterations in renal tubular epithelial cells after burn injury. Renal tubular injury scores and the average optical density score of kidney injury molecule-1 (KIM-1) immunohistochemical staining in the MG53-treated group were significantly lower than those in control group (P < 0.001). Exogenous rhMG53 was found to be located in renal tubular epithelial cells. Numerous polymerase I and transcript release factor (PTRF) were expressed in the mouse kidney after severe scalding. In conclusion, our data indicate that MG53 protein protects the kidney by involving local PTRF after severe burn injury.