Prognostic value of receptor tyrosine kinases in malignant melanoma patients: A systematic review and meta-analysis of immunohistochemistry.

Background: Substantial evidence suggests that receptor tyrosine kinases (RTKs) are overexpressed in tumors; however, few studies have focused on the prognostic value of RTKs in melanoma. Objectives: The objective of this study is to evaluate the association between overexpression of RTKs and survival in melanoma patients based on immunohistochemistry (IHC) analysis. Methods: Our review is registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42021261460. Seven databases were searched, and data were extracted. We used IHC to measure the association between overexpression of RTKs and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and clinicopathology in melanoma patients. Pooled analysis was conducted to assess the differences between Hazard Ratios along with 95% confidence intervals. Results: Of 5,508 publications examined following the database search, 23 publications were included in this study, which included data from a total of 2,072 patients. Vascular endothelial growth factor receptor 2 (VEGF-R2) overexpression was associated with worse OS and DFS in melanoma. Furthermore, there was an association between OS and the expression of several RTKs, including epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition factor (MET), vascular endothelial growth factor receptor 1 (VEGF-R1), and insulin-like growth factor 1 receptor (IGF-1R). There were no significant correlations between EGFR overexpression and worse DFS or PFS. EGFR overexpression was associated with worse OS cutaneous and nasal melanoma, but not uveal melanoma. However, MET overexpression was related to worse OS in both cutaneous and uveal melanoma. Furthermore, EGFR overexpression was associated with a worse OS in Europe compared to other geographic areas. Moreover, EGFR and MET overexpression showed significant prognostic value in patients with the cut-off "≥10% staining". Conclusions: Our findings build concrete evidence that overexpression of RTKs is associated with poor prognosis and clinicopathology in melanoma, highlighting RTK expression has the potential to inform individualized combination therapies and accurate prognostic evaluation.

Interplay between Extracellular Matrix and Neutrophils in Diseases.

The extracellular matrix (ECM) is a highly dynamic and complex network structure, which exists in almost all tissues and is the microenvironment that cells rely on for survival. ECM interacts with cells to regulate diverse functions, including differentiation, proliferation, and migration. Neutrophils are the most abundant immune cells in circulation and play key roles in orchestrating a complex series of events during inflammation. Neutrophils can also mediate ECM remodeling by providing specific matrix-remodeling enzymes (such as neutrophil elastase and metalloproteinases), generating neutrophil extracellular traps, and releasing exosomes. In turn, ECM can remodel the inflammatory microenvironment by regulating the function of neutrophils, which drives disease progression. Both the presence of ECM and the interplay between neutrophils and their extracellular matrices are considered an important and outstanding mechanistic aspect of inflammation. In this review, the importance of ECM will be considered, together with the discussion of recent advances in understanding the underlying mechanisms of the intricate interplay between ECM and neutrophils. A better comprehension of immune cell-matrix reciprocal dependence has exciting implications for the development of new therapeutic options for neutrophil-associated infectious and inflammatory diseases.

Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps Formation.

Excessive neutrophil extracellular trap (NET) formation is an important contributor to sepsis-induced acute lung injury (ALI). Recent reports indicate that platelets can induce neutrophil extracellular trap formation. However, the specific mechanism remains unclear. Tph1 gene, which encodes the rate-limiting enzyme for peripheral 5-hydroxytryptophan (5-HT) synthesis, was knocked out in mice to simulate peripheral 5-HT deficiency. Cecal ligation and puncture (CLP) surgery was performed to induce sepsis. We found that peripheral 5-HT deficiency reduced NET formation in lung tissues, alleviated sepsis-induced lung inflammatory injury, and reduced the mortality rate of CLP mice. In addition, peripheral 5-HT deficiency was shown to reduce the accumulation of platelets and NETs in the lung of septic mice. We found that platelets from wild-type (WT), but not Tph1 knockout (Tph1 -/- ), mice promote lipopolysaccharide (LPS)-induced NET formation. Exogenous 5-HT intervention increased LPS-induced NET formation when Tph1 -/- platelets were co-cultured with WT neutrophils. Therefore, our study uncovers a mechanism by which peripheral 5-HT aggravated sepsis-induced ALI by promoting NET formation in the lung of septic mice.

[Peripheral 5-hydroxytryptophan aggravates lung injury in septic mice by inducing the formation of neutrophils extracellular trap].

OBJECTIVE: To observe the effect of peripheral 5-hydroxytryptophan (5-HT)-induced neutrophil extracellular trap (NET) on lung injury in septic mice. METHODS: Wild-type (WT type) and Tph1 knockout (KO) C57 mice (6-8 weeks) were selected and divided into WT mice sham group, WT mice sepsis group, Tph1KO mice sham group and Tph1KO mice sepsis group according to the random number table method. Mice in the sham group received sham surgery (only open the abdominal cavity to flip the cecum without ligation and puncture, and then close the abdominal cavity); the mice in the sepsis group received cecal ligation and perforature (CLP) to establish sepsis model. The mice were sacrificed 12 hours after the operation, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in bronchialalveolar lavage fluid (BALF) were detected by enzyme linked immunoadsordent assay (ELISA); at the same time, the lung tissues were collected, and the pathological changes of lung tissues were observed under light microscope, and the production of NET in lung tissues was observed by immunofluorescence microscope. RESULTS: The pathological results suggested that the lung tissue structure in sham groups was intact without exudation, while the alveolar structures of mice in the sepsis groups were damaged, with obvious exudation in the alveolar cavity and thickened alveolar walls accompanied by a large number of inflammatory cell infiltration, and the degree of lung injury in the sepsis group of WT mice was more severe than that of the sepsis group of Tph1KO mice. ELISA results showed that there was no statistically significant difference in the contents of TNF-α and IL-6 in mice BALF from different strains of the sham group; while the contents of TNF-α and IL-6 in BALF of septic mice group were significantly higher than those in sham group [WT mice: TNF-α (µg/L) was 158.20±28.46 vs. 14.00±3.28, IL-6 (µg/L) was 304.98±21.78 vs. 57.70±12.30; Tph1KO mice: TNF-α (µg/L) was 85.88±20.13 vs. 14.95±1.53, IL-6 (µg/L) was 169.50±45.61 vs. 55.05±12.68, all P < 0.01], and the above index levels in the sepsis group of WT mice were significantly higher than the sepsis group of Tph1KO mice [TNF-α (µg/L): 158.20±28.46 vs. 85.88±20.13, IL-6 (µg/L): 304.98±21.78 vs. 169.50±45.61, both P < 0.01]. Immunofluorescence staining showed that a very small amount of NET formation was detected in the mice lungs from the sham group; a large amount of NET formation was detected in the lung tissues in the sepsis group, which were significantly higher than those in sham group [WT mice: (34.75±7.27)% vs. (1.75±0.96)%, Tph1KO mice: (14.25±5.74)% vs. (2.50±1.29)%, both P < 0.01], and the amount of NET produced in the lung tissues of the WT mice sepsis group was significantly higher than that of the Tph1KO mice sepsis group [(34.75±7.27)% vs. (14.25±5.74)%, P < 0.01]. CONCLUSIONS: In sepsis, the increased production of inflammatory factors in the mice lung tissues induces to lung injury. The mechanism may relate to the increased production of NET in the lung tissues mediated by peripheral 5-HT synthesized by enterochromaffin cells and released into the blood; inhibiting the production of 5-HT in the peripheral blood can effectively reduce the production of NET in the lung tissues, thereby reducing lung injury.

Management of a Man With Hydrofluoric Acid Burns: A Case Report and Review.

A hydrofluoric acid (HFA) burn is a severe condition with the characteristics of acute onset, rapid progression, and high complication and mortality rates. Emergency and systemic treatments are especially important for major HFA burns. The author presents the case of a 46-year-old man burned by the spillage of HFA at a high concentration (45-50%). He suffered burns over 30% of his total body area (5% deep partial-thickness burns and 25% third-degree burns). Debridement, tangential excision, and electrolyte therapy were quickly performed for urgent treatment. Symptomatic treatment was sustained to address severe complications and recurrent injury. For successful management, the patient was stabilized, and he exhibited complete wound repair after 3 months. The author summarizes severe cases of HFA burns to emphasize the difficulty of treatment. The existing approved therapies and complications are discussed, and the significance of electrolyte disorders, especially hypocalcemia, is highlighted. The pathophysiology of HFA burns and recommendations for the treatment of HFA burns at different sites are presented to provide a relatively complete treatment guideline focused on electrolyte disorders.

Mandibular oblique ostectomy: an alternative procedure to reduce the width of the lower face.

BACKGROUND: Mandibular angle ostectomy and mandibular angle-splitting ostectomy are the main surgical approaches for correction of a square and broad lower face. However, based on our clinical experience, these approaches have some limitations. We improved the ostectomy as an intraoral-approach oblique ostectomy to reduce the width of the lower face, such that the mandibular contour satisfied both surgeons and patients. METHODS: Between 2007 and 2008, 11 patients who underwent bilateral mandible oblique ostectomy for a square and broad lower face at the craniofacial center in Renji Hospital were involved in the study. At the prominent angle of the mandible, the outer cortex was resected through an intraoral approach. Final results showed that the lower-face width appeared to be decreased, and a natural mandible contour was achieved. All the patients were followed up for at least 6 months. RESULTS: All the patients were very pleased with their postoperative frontal and lateral view. Transient marginal mandibular branch palsy occurred in 1 patient, who ultimately recovered later. There were no other complications. CONCLUSION: Intraoral-approach oblique ostectomy can make the face look thinner from the frontal view and, in the lateral view, keep the natural contour of the mandibular angle. This technique is also easy to put into practice, saves time, and has fewer complications. We consider the oblique ostecomy technique as a safe and effective treatment for mandibular contouring.

[Effect of botulinum toxin type A injection on hypertrophic scar in rabbit ear model].

OBJECTIVE: To investigate the effect of botulinum toxin type A (Botox A) injection on hypertrophic scar in rabbit ear model. METHODS: The hypertrophic scar model was established in 16 Japanese rabbits' ears. These wounds were divided into two groups as group T (treated with Botox A, n = 48) and group S (not treated, n = 48). The wounds healing times and scar hypertrophy were observed with 8 specimen of normal skin at the rabbit ears as sham group B. HE stain was used to assess the hypertrophic index (HI). The expression of collagen I and III was tested by western-blot. The cell cycle of fibroblasts was studied by flow cytometry. RESULTS: The HI was significantly lower in group T than in group S (P < 0.01). The expression of collagen I and III, as well as the ratio of I to III, was markedly stronger in group S than in group T (P < 0.01). Compared with group T, more fibroblasts were in G2-M in group S and fewer in G0-G1 (P < 0.05). CONCLUSIONS: Local injection of Botox A can inhibit the formation of hypertrophic scar and the activity of fibroblasts in rabbit ear model. It can significantly decrease the expression of collagen I and III in hypertrophic scar, as well as the ratio of collagen I to III. It serves as the basis for the treatment of hypertrophic scar with Botox A.

[Effect of botulinum toxin type A on the expression of substance P, calcitonin gene-related peptide, transforming growth factor beta-1 and alpha smooth muscle actin A in wound healing in rats].

OBJECTIVE: To investigate the effect of botulinum toxin type A on the expression of substance P (SP), calcitonin gene-related peptide (CGRP), transforming growth factor beta-1 (TGF-beta1) and alpha smooth muscle actin A (alpha-SMA) in wound healing. METHODS: 60 rats were randomly divided into group C (control) group L (low-dose) and group H (high-dose), with 20 rats in each group. The wound-healing model was established by excision of four full-thickness skin (1 cm x 1 cm, around the injection site) on the back of all SD rats on the 7th day after BTA injection. The wound size was measured and the expression of SP, CGRP, TGF-beta1 and alpha-SMA in wound granulation tissue was assayed by immunohistochemical staining and computerized image analysis before operation, and 3 days, 7 days and 14 days after operation. RESULTS: All the wounds healed 14 days after operation. The wound size in L and H group was not significantly different with that in C group on the 3rd day and 7th day after operation. The positive immuno-staining of SP, CGRP, TGF-beta1 and alpha-SMA in group L and H was significantly weaker than those in C group. Meanwhile, the positive immuno-staining of all above substances in H group was weaker than those in L group significantly. CONCLUSIONS: Botulinum toxin type A can decrease the expression of SP, CGRP, TGF-beta1, and alpha-SMA in wound healing in a dose-dependent manner with no effect on the healing time.