Parecoxib sodium attenuates acute lung injury following burns by regulating M1/M2 macrophage polarization through the TLR4/NF-κB pathway.

High temperature-induced burn injury often leads to an excessive inflammatory cascade resulting in multiple organ dysfunction syndrome, such as acute lung injury (ALI), in addition to skin tissue damage. As a specific COX2 inhibitor, parecoxib sodium suppresses the inflammatory response during burn injury. The effect of parecoxib sodium on ALI induced by burn injury and the associated molecular mechanism still need to be investigated. The role of parecoxib sodium in burn injury-induced ALI through the TLR4/NF-κB pathway was explored in the present study. A burn-induced ALI mouse model was constructed, and M1/M2 macrophages in lung tissue and markers involved in the TLR4/NF-κB signalling pathway were evaluated in bronchoalveolar lavage fluid (BALF) and MH-S mouse alveolar macrophages in vitro. The results indicated that parecoxib sodium attenuated lung injury after burn injury, decreased iNOS and TNF-α expression, increased IL-10 expression in BALF, and regulated the CD86-and CD206-mediated polarization of M1/M2 macrophages in lung tissue along with MH-S mouse alveolar macrophages. The effect of parecoxib sodium might be reversed by a TLR4 agonist. Overall, the results suggested that parecoxib sodium can regulate the polarization of M1/M2 macrophages through the TLR4/NF-κB pathway to attenuate ALI induced by skin burns.

Fatalism as a Mediator of the Association Between Family Resilience and Self-Management Among Patients with Chronic Wounds in China.

Purpose: The purpose of this study was to examine how fatalism acts as a mediator in the correlation between family resilience and self-management among patients with chronic wounds in China. Participants and Methods: This study used a cross-sectional research design. A total of 269 adult patients (18-94 years old) with chronic wounds residing in Wuxi, China participated in this study. Participants completed the Chinese version of the Walsh Family Resilience Questionnaire, 16-item Chinese version of the Fatalism Scale, and Self-Management Scale of Chronic Wound Patients. We conducted correlation and mediation analyses using SPSS 27.0 and PROCESS 4.0. Results: The results indicated family resilience was a significant positive predictor of self-management (ß = 0.7101, p < 0.0001), and the pathway between family resilience and self-management was partially mediated by fatalism (Effect = 0.1432, 95% confidence interval [0.0625, 0.2341]). Conclusion: The results indicated that incorporating spiritual interventions into future person-centered self-management programs could align with the motivation of patients with chronic wounds and their families, and reduce the negative impact of fatalism on health outcomes.

Fabrication of biologically inspired electrospun collagen/silk fibroin/bioactive glass composited nanofibrous to accelerate the treatment efficiency of wound repair.

A triple-layer matrix Collagen/Silk fibroin/Bioactive glass composited Nanofibrous was fabricated by linking electrospinning and freeze-drying systems, this typical three layered composite with a nanofibrous fragment as the key (top) layer, middle portion as inferior, and a spongy porous fragment as the third (bottom) deposit to develop the synergistic effect of composite materials resultant to physical and biological performances. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy were used to assess the final material's physicochemical properties (SEM). The triple-layer matrix had a nanofibrous and porous structure, which has qualities including high porosity, swelling, and stability, which are important in soft-tissue engineering. NIH 3 T3 fibroblast and humanoid keratinocyte (HaCaT) cell lines were also used to investigate the matrix's in vitro biological and fluorescent capabilities, which showed excellent cell adherence and proliferation across the composite layers. The synergistic arrangement of nanofibrous substantial deposition onto collagenous with silk fibroin candidates has therefore proven effective in the construction of a tri-layer matrix for skin-tissue-engineering applications.

Application of Comfort Therapy under eCASH Concept in Acute and Chronic Wound Treatment.

INTRODUCTION: Given the new ideas on wound care offered by the eCASH (early Comfort using Analgesia, minimal Sedatives, and maximal Humane care) and the substantial differences in clinical treatment between acute and chronic wounds, we aimed to investigate the effect of comfort therapy under the eCASH concept on analgesic sedation and accelerated wound healing in patients with acute or chronic wounds. METHODS: This randomized clinical study was conducted in two parts: acute wounds and chronic wounds. Patients with acute wounds were allocated into the acute wound control group (AWCG) and the acute wound experimental group (AWEG). Patients with chronic wounds were allocated into the chronic wound control group (CWCG) and two experimental groups, in which they received intermittent negative pressure therapy (IPTEG) and continuous negative pressure therapy (CPTEG). On the basis of the standard treatment for patients in the control group, eCASH therapy was used in the experimental groups. In addition, pain intensity and procedural anxiety were evaluated using the visual analogue score (VAS) and the Hamilton Anxiety Scale (HAM-A). In addition, clinical effects were assessed on the basis of the size of the surface area, rate of healing, and concentration of pro-inflammatory factors (IL-1, IL-6, TNF-α) and growth factors (VEGF, bFGF, TGF-ß1). RESULTS: Compared with the control group, the VAS score and HAM-A score in the experimental groups were significantly decreased after intervention (P < 0.05). After intervention, the levels of IL-1ß, IL-6, and TNF-α in AWEG, IPTEG, and CPTEG were significantly lower than those in AWCG. In addition, the levels of VEGF, bFGF, and TGF-ß1 in IPTEG and CPTEG were significantly higher than those in CWCG (P < 0.05). CONCLUSION: These results indicated that comfort therapy under the eCASH concept has a significant effect on ameliorating the pain and anxiety of patients, reducing the inflammatory reaction during the period of wound healing in the treatment of acute and chronic wounds. CLINICAL TRIAL REGISTRY: The trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200057981).

eCASH concept-based care for patients with small-area burns: a pilot randomized controlled trial.

BACKGROUND: Small-area burn is a common but specific type of injury that can still lead to serious complications if not managed properly. Researchers have introduced a number of interventions. OBJECTIVE: The objective of this study was to compare the effects of eCASH concept-based care (ie, eBCare) with those of standard treatment on wound healing in patients with small-area burns. METHODS: In this prospective randomized controlled trial, patients with small-area burns received either eBCare (n = 35) or standard burn treatment (n = 35) for 2 weeks. Pain, anxiety, heart rate, exudate, and wound area were measured during and after dressing changes. Scar color and thickness were assessed 4 years or longer after discharge. RESULTS: The eBCare group had a lower median pain score, anxiety score, and heart rate compared with the control group (P < .001). The eBCare group also had a higher median wound healing rate on day 14 than the control group (P < .05). At follow-up 4 years or more after discharge, the eBCare group had better scar color and thickness than the control group (P < .05). CONCLUSION: The use of eBCare reduced pain and anxiety, accelerated wound healing, and improved scar outcomes in patients with small-area burns, which suggests that eBCare may be a feasible option for this population.

Unilateral Sciatic Nerve Crush Induces White Blood Cell Infiltration of the Contralateral Nerve.

Nerve injury leads to the accumulation of white blood cells derived from the bone marrow in the lesioned nerve, but it is still unknown whether there are similar responses in unlesioned nerves. To address this question, sciatic nerves of mice expressing enhanced green fluorescent protein (EGFP) in their bone marrow were crushed unilaterally to observe the invasion of bone marrow-derived cells into the contralateral unlesioned nerve. Two days after surgery, EGFP+ cells began to infiltrate both the damaged and undamaged nerves. These cells gradually amplified to the highest point within 14 days and slowly lowered. In ipsilateral (lesioned) and contralateral (unlesioned) nerves, the time course of infiltration of EGFP+ cells was similar, but the magnitude was much less for the unlesioned one. Through CD68 staining, some cells were identified as macrophages. Transmission electron microscopy revealed slight demyelination and phagocytosing macrophages in the contralateral nerve. The data showed that infiltration by white blood cells is a response to nerve injury, even in uninjured nerves.

Fabrication of homogeneously-aligned nano-fillers encapsulated silk fibroin electrospun nanofibers for improved fibroblast attachment, epithelialization, and collagen depositions: in vitro and in vivo wound healing evaluation.

Curcumin (CUR), a natural compound found in turmeric that has multiple biological functions such as antibacterial, anti-oxidant, anti-cancer, and wound healing properties due to its hydrophobicity CUR solubilization is a great challenge. In this study, the electrospinning process is used to fabricate a novel active wound dressing based on CUR loaded silk fibroin (SF)/hydroxyapatite (HAp) (SF/HAp-CUR) nanofibers in diabetic rats. The incorporation of CUR into the SF/HAp-CUR nanofibers had an obvious effect on the morphology and dimension of SF/HAp-CUR nanofibers characterized by SEM analysis. Morphological analysis revealed that the average fiber diameter of the SF/HAp, SF/HAp-CUR(1.0%), SF/HAp-CUR(3.0%), and SF/HAp-CUR(5.0%) nanofibers were calculated to be 461 ± 65 nm, 323 ± 90 nm, 412 ± 110, and 497 ± 118 nm. In addition of CUR in the SF/HAp nanofibers significantly improved the mechanical properties in terms of enhanced elongation at break and tensile strengths. The percentages of water uptake and porosity of SF/HAp-CUR nanofibers were 143.7 ± 4.05% and 92.5 ± 3.40%, respectively. The results showed that CUR presented a sustained release behavior from SF/HAp-CUR nanofibers and maintained its free radical scavenging ability. The prepared nanofibers surface interaction was confirmed by FT-IR and XRD analysis. Antibacterial tests revealed SF/HAp-CUR on day 14 improved the bacterial embarrassment of both E. coli and S. aureus by 4 to 5-fold, respectively. The cell cytotoxicity with L929 mouse fibroblasts on the SF/HAp-CUR nanofibers was very low at 7.7 ± 1.75% on day 14. In vivo wound healing showed that the treatment using SF/HAp-CUR nanofibers significantly increased the rate of wound closure (99.6 ± 0.86%) on day 21 compared with that using SF/HAp nanofibers (67.7 ± 4.25%). These results showed that the delivery of SF/HAp-CUR nanofibers can facilitate antibacterial, anti-oxidant, cytotoxicity of wound healing properties.

Fluid resuscitation based on pulse contour cardiac output monitoring is associated with improved prognosis in adult severe burn patients: a retrospective cohort study.

BACKGROUND: A monitoring method is needed to further guide fluid resuscitation in severe burn injury. This study was performed to investigate the effects of pulse contour cardiac output (PCCO) monitoring on the prognosis of adult severe burns patients. METHODS: We conducted a retrospective study enrolling patients from January 2015 to December 2020, who were divided into a control group receiving conventional monitoring and a study group receiving PCCO monitoring. The primary outcomes were 28-day mortality and total mortality, and the secondary outcomes included burn-related complications and the length of hospital stay and ICU stay. Multivariable logistic regression analysis and linear regression analysis were performed to determine the risk factors of burns-related complications and length of hospital stay in enrolled patients. RESULTS: A total of 109 patients in the control group and 82 patients in the study group were enrolled. While the area of full thickness burn was much higher in the control group than in the study group (P=0.021), no significant difference was found in other characteristics between the two groups. During fluid resuscitation, the fluid volume ratio of the study group was significantly different from that of the control group, and both in the first 24 hours and the second 24 hours, the resuscitation fluid volume ratio and colloid volume ratio was significantly higher in the control group than in the study group (all P<0.001). Eight patients died during treatment, and there were more patients experiencing AKI and ARDS in the control group than in the study group (P=0.029 and 0.016). The lengths of hospital stay and ICU stay in the study group was much shorter than in the control group (P<0.001 and 0.005). In addition, TBSA was an important risk factor for both AKI and ARDS, and the existence of inhalation injury and older age increased the incidence of ARDS. Higher TBSA, inhalation injury, and burn-related complications were related to longer hospital stay in enrolled patients. CONCLUSIONS: Fluid resuscitation according to PCCO monitoring can effectively reduce the volume of colloid and overall fluid volume and reduce the incidence of burns-related complications and shorten the length of hospital stay.

Effect of interleukin-8 receptor B (IL8RB) rs1126579 C>T variation on the risk to cancer.

Chemokines are a type of cytokine that participate in the migration of macrophages and monocytes to inflammatory cells. In particular, CXC chemokines are involved in the development of many cancers. Evidence for the association between interleukin-8 receptor B (IL8RB) rs1126579 C > T variation and cancer risk remains contradictory. Here, we utilized a comprehensive analysis containing odds ratios (ORs), regression, and in silico tools to evaluate the effect of IL8RB polymorphism on cancer risk. We further employed Gene set enrichment analysis combined with ELISA to evaluate the IL8RB expression in patients with prostate cancer (PRAD). A total of 5,187 cancer cases and 6,691 controls were included in the present analysis. Individuals with the TT genotype were associated with an increased risk of cancer compared to those with the TC+CC genotype. In a subgroup analysis by type of cancer, individuals with the TT genotype had a 39% increased risk of urinary cancer compared to those with the CC genotype. A subgroup analysis by ethnicity showed that Asians carrying the TC genotype had a 26% lower risk of cancer than those carrying the CC genotype. We found that the expression of IL8RB was down-regulated in PRAD. Compared to that in PRAD subjects carrying the CC genotype, the expression of IL8RB was decreased in patients with the TT+TC genotype. In conclusion, the IL8RB rs1126579 C > T variation may be associated with cancer risk, especially in Asian populations and patients with PRAD.

Emerging Role of IL-10 in Hypertrophic Scars.

Hypertrophic scars (HS) arise from traumatic or surgical injuries and the subsequent abnormal wound healing, which is characterized by continuous and histologically localized inflammation. Therefore, inhibiting local inflammation is an effective method of treating HS. Recent insight into the role of interleukin-10 (IL-10), an important anti-inflammatory cytokine, in fibrosis has increased our understanding of the pathophysiology of HS and has suggested new therapeutic targets. This review summarizes the recent progress in elucidating the role of IL-10 in the formation of HS and its therapeutic potential based on current research. This knowledge will enhance our understanding of the role of IL-10 in scar formation and shed new light on the regulation and potential treatment of HS.

GDC-0084 inhibits cutaneous squamous cell carcinoma cell growth.

GDC-0084 is a novel and potent small-molecule PI3K-mTOR dual inhibitor. The present study examined its potential activity in cutaneous squamous cell carcinoma (cSCC) cells. Our results show that GDC-0084 treatment at nanomole concentrations potently inhibited survival and proliferation of established (A431, SCC-13 and SCL-1 lines) and primary human cSCC cells. GDC-0084 induced apoptosis activation and cell cycle arrest in the cSCC cells. It was more efficient than other known PI3K-Akt-mTOR inhibitors in killing cSCC cells, but was non-cytotoxic to the normal human skin fibroblasts/keratinocytes. In A431 cells and primary cSCC cells, GDC-0084 blocked phosphorylation of key PI3K-Akt-mTOR components, including p85, Akt, S6K1 and S6. GDC-0084 also inhibited DNA-PKcs activation in cSCC cells. Significantly, restoring DNA-PKcs activation by a constitutively active-DNA-PKcs (S2056D) partially inhibited GDC-0084-induced cell death and apoptosis in A431 cells. In vivo, GDC-0084 daily gavage potently inhibited A431 xenograft tumor growth in mice. In GDC-0084-treated tumor tissues PI3K-Akt-mTOR and DNA-PKcs activation were significantly inhibited. In summary, GDC-0084 inhibits human cSCC cell growth in vitro and in vivo through blocking PI3K-Akt-mTOR and DNA-PKcs signalings.

Roles of p300 and cyclic adenosine monophosphate response element binding protein in high glucose-induced hypoxia-inducible factor 1α inactivation under hypoxic conditions.

AIMS/INTRODUCTION: Given the high prevalence of diabetes and burn injuries worldwide, it is essential to dissect the underlying mechanism of delayed burn wound healing in diabetes patients, especially the high glucose-induced hypoxia-inducible factor 1 (HIF-1)-mediated transcription defects. MATERIALS AND METHODS: Human umbilical vein endothelial cells were cultured with low or high concentrations of glucose. HIF-1α-induced vascular endothelial growth factor (VEGF) transcription was measured by luciferase assay. Immunofluorescence staining was carried out to visualize cyclic adenosine monophosphate response element binding protein (CREB) localization. Immunoprecipitation was carried out to characterize the association between HIF-1α/p300/CREB. To test whether p300, CREB or p300+CREB co-overexpression was sufficient to rescue the HIF-1-mediated transcription defect after high glucose exposure, p300, CREB or p300+CREB co-overexpression were engineered, and VEGF expression was quantified. Finally, in vitro angiogenesis assay was carried out to test whether the high glucose-induced angiogenesis defect is rescuable by p300 and CREB co-overexpression. RESULTS: Chronic high glucose treatment resulted in impaired HIF-1-induced VEGF transcription and CREB exclusion from the nucleus. P300 or CREB overexpression alone cannot rescue high glucose-induced HIF-1α transcription defects. In contrast, co-overexpression of p300 and CREB dramatically ameliorated high glucose-induced impairment of HIF-1-mediated VEGF transcription, as well as in vitro angiogenesis. Finally, we showed that co-overexpression of p300 and CREB rectifies the dissociation of HIF-1α-p300-CREB protein complex in chronic high glucose-treated cells. CONCLUSION: Both p300 and CREB are required for the function integrity of HIF-1α transcription machinery and subsequent angiogenesis, suggesting future studies to improve burn wound healing might be directed to optimization of the interaction between p300, CREB and HIF-1α.

Advancement of maxillary anterior segment by distraction osteogenesis for severe maxillary retrusion in cleft lip and palate.

BACKGROUND: Maxillary anterior segmental distraction osteogenesis (MASDO) is a recently used method for correction of severe maxillary retrusion in cleft lip and palate (CLP) patients. In this article, we evaluated the feasibility of MASDO using rigid external distraction (RED) and rapid orthodontic tooth movement to correct severe maxillary retrusion in CLP patients. METHODS: Fourteen male and five female complete CLP patients between the ages of 18 and 22 years (mean age 19.7 years) at the time of distraction, with severe maxillary retrusion, were treated with the rigid external distraction (RED) device after maxillary anterior osteotomy. Rapid orthodontic tooth movement was started one week after the MASDO. Standard profile photographic, cephalometric films were obtained preoperatively and after therapy. Sella-nasion-point A (SNA) and Sella-nasion-point B (SNB) angles were measured to reflect changes in maxillary and mandibular position, and the distance between anterior nasal spine and posterior nasal spine (ANS-PNS) was measured to represent the maxillary dental arch length. RESULTS: The SNA angle increased from an average of 74.6° (range 73.0°-78.0°), preoperatively, to 83.4° (range 78.6°-88.0°) after the RED was removed (P < 0.01). All cases of severe maxillary retrusion were improved. Nine patients' profiles became harmonious after therapy. One patient had a bimaxillary protrusion deformity and needed further surgery. The regenerate alveolar crest and edentulous space on both segments was almost completely eliminated after rapid orthodontic tooth movement. CONCLUSION: MASDO with the RED system and rapid orthodontic tooth movement is a successful way of correcting severe maxillary retrusion in CLP patients.

The middle-forearm flap based on perforator of ulnar artery for electrical burn wound on the wrist / 中华整形外科杂志

<p><b>OBJECTIVE</b>To dicuss the application and therapeutic effect of middle-forearm flap based on perforator of ulnar artery for electrical burn wound on the wrist.</p><p><b>METHODS</b>From Oct. 2009 to Oct. 2012, 10 cases of electrical burn wounds on the wrist were treated. A line from radialis medial epicondyle of humerus to the interior radialis pisiform bone was connected as flap axis. At the midpoint of the line, Doppler flow imaging meter was used to detect the emerging point of perforator vessel. The flap was designed and harvested. The flap was transferred reversely, with superficial vein retaining which was anastomosed with vein at recipient sites in 3 cases. The wounds in the donor sites were closed directly in 2 cases, and with skin graft in 8 cases.</p><p><b>RESULTS</b>All the 10 flaps survived completely. 7 cases without vein anastomosis underwent obvious flap edema during 2-4 days postoperatively, which resovled 1 week later. Sub-flap tissue necrosis and infection happened in 2 cases, which healed after dressing and drainage. Patients were followed up for 3-36 months with satisfactory results.</p><p><b>CONCLUSIONS</b>The middle-forearm flap based on perforator of ulnar artery has a stable and reliable blood supply. It offers a new choice for the electric burn wound on the wrist, especially at the ulnar side.</p>

[Repair contracture deformity of perineal scar caused by burn with extra long scapular-lateral thoracic-ilioinguinal Siamese flap].

OBJECTIVE: To assess the efficacy of the extra long scapular-lateral thoracic-ilioinguinal siamese flap to repair the contracture deformity of perineal scar caused by burn and to discuss its characteristics. METHODS: From January 2008 to August 2009, 9 patients with contracture deformity of perineal scar after deep II degree to III degree burn were treated. There were 7 males and 2 females aged from 22 to 54 years (35.4 years on average). The course of disease ranged from 8 months to 5 years. All cases had central type of perineal scar. Among the cases, 3 cases were complicated by abdominal scar, 4 cases by legs scar, and 2 cases by abdominal and legs scar. Scar ulcer was observed in 2 cases. The opening-closing angle of bilateral lower extremities was (29.4 +/- 8.8) degrees. And anus could not expose entirely so that squatting and relieving the bowels were difficult in 6 cases. Defect areas after scar resection ranged from 20 cm x 6 cm to 28 cm x 8 cm. The size of extra long scapular-lateral thoracic-ilioinguinal siamese flap ranged from 35 cm x 12 cm to 58 cm x 15 cm. The donor sites were sutured directly. RESULTS: Blister and necrosis occurred in 1 case and was cured after dressing changed, and others flaps survived with wounds primary healing. Incision at donor site healed by first intention. All cases were followed up 6-12 months. The perineal function improved and the partial deformities were corrected. The opening-closing angle of bilateral lower extremities increased to (75.6 +/- 11.3) degrees, showing significant difference between pre- and post-operation (P < 0.05). The functions of squatting and relieving the bowels recovered well. The perineal scar adhesion recurred in 2 cases after 6 months of operation and were cured after scar resection and expanding flaps transposition. CONCLUSION: In view of large donating region, great facility for transposition, stable and sufficient blood supply, reutilization as expanded flap, it was an effective treatment and a beneficial trial by applying the transposition of the extra long scapular-lateral thoracic-ilioinguinal siamese flap for contracture deformity of perineal scar caused by burn.