Long noncoding RNA XIST promotes cell proliferation and migration in diabetic foot ulcers through the miR-126-3p/EGFR axis.

BACKGROUND: The prevalence of diabetic foot ulcers (DFUs) has caused serious harm to human health. To date, a highly effective treatment is lacking. Long noncoding RNA X-inactive specific transcript (lncRNA XIST) has been the subject of mounting research studies, all of which have found that it serves as a protective factor against certain diseases; however, its function in DFUs is not entirely understood. This study was performed to determine the importance of the lncRNA XIST in the pathogenesis and biological function of DFUs. METHODS: Diabetic ulcer skin from rats was analysed using haematoxylin-eosin (HE), Masson's trichrome, and immunohistochemistry (IHC) staining. The differences in the expression of genes and proteins were examined with real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Next, the interaction was verified with a dual luciferase gene reporter assay. In addition, CCK-8, Transwell, and wound healing assays were used to assess the proliferation and migration of HaCaT cells. RESULTS: The lncRNA XIST and epidermal growth factor receptor (EGFR) were downregulated, while microRNA-126-3p (miR-126-3p) was increased in diabetic ulcer rat skin tissues and high glucose-induced HaCaT cells. In addition, we found that the lncRNA XIST binds to miR-126-3p and that EGFR is directly targeted by miR­126­3p. Silencing XIST contributed to upregulated miR-126-3p expression, thus lowering EGFR levels and inhibiting the proliferative and migratory abilities of high glucose-treated HaCaT cells; however, the miR-126-3p inhibitor and overexpression of EGFR reversed this effect. CONCLUSION: Decreased lncRNA XIST expression inhibits the proliferative and migratory abilities of high glucose-induced HaCaT cells by modulating the miR-126-3p/EGFR axis, causing delayed wound healing.

Effect of peripheral nerve block versus general anesthesia on the hemodynamics and prognosis of diabetic patients undergoing diabetic foot Surgery.

BACKGROUND: Diabetic foot ulcers (DFUs) represent a significant foot-related concern for patients with multiple co-morbidities, and surgical intervention is often employed. Notably, peripheral nerve block anesthesia (PNB) has emerged as a new approach for the surgical management of DFUs, providing sustained hemodynamic stability and superior postoperative pain control compared to general anesthesia (GEA). METHODS: The present study utilized a retrospective analysis of hospitalized patients who met the inclusion criteria for DFUs over a period of 7 years. Patients were categorized into two groups based on the type of anesthesia employed during the procedure: GEA or PNB. Extensive patient information was gathered and analyzed, such as demographics, intraoperative hemodynamic parameters, numeric rating scale (NRS) scores, and healing outcomes. The preliminary results assessed in this study were intraoperative hemodynamic stability and postoperative analgesic efficacy. RESULTS: During the study period, 117 patients received surgical therapy based on GEA, while 145 patients received PNB. Notably, the mean intraoperative blood pressure was significantly lower in the GEA group, and this difference remained statistically significant even after Bonferroni adjustment using linear mixed models. Additionally, the frequency of hypotensive episodes was higher in the GEA group (P < 0.05). Furthermore, the perioperative transfusion volume, overall intraoperative fluid input, and intraoperative bleeding volume were significantly more significant in the GEA group than in the PNB group. The postoperative pain NRS scores differed considerably between the two groups (Bonferroni corrected P < 0.01), with the GEA group exhibiting higher opioid consumption on the day of surgery and the first postoperative day when using patient-controlled intravenous analgesia (PCIA). Supplemental analgesic medication was more significant in the GEA group 24 h postoperatively. However, the two groups had no difference in hospital stay or treatment outcomes. There was no difference between the two groups regarding secondary surgery and amputation procedures. Although the 5-year mortality rate is 30.5%, no significant difference in mortality rates between the two groups was observed. CONCLUSIONS: Compared to GEA, PNB is a safe and effective alternative therapy for managing DFUs. Our findings suggest that PNB administration during surgical intervention for this condition results in more stable intraoperative hemodynamics and superior postoperative analgesic effects, despite no significant difference in overall treatment outcomes between the two groups. The two groups did not differ in re-surgery, amputation, or 5-year mortality.

Negative-pressure wound therapy in skin grafts: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Although skin grafts are widely used in reconstruction of large skin defect and complex wounds, many factors lead to suboptimal graft take. Negative-pressure wound therapy (NPWT) reportedly increases the graft take rates when added to skin grafting, but a summary analysis of the data of randomized controlled trials has yet to be performed. We conducted this systematic review and meta-analysis of randomized controlled trials to compare the effectiveness and safety of NPWT and non-NPWT for patients with skin grafts. METHODS: We searched PubMed, Embase, Cochrane Library, and CNKI for relevant trials based on predetermined eligibility criteria from database establishment to February 2020. Two reviewers screened citations and extracted data independently. The quality of the included studies was evaluated according to the Cochrane Handbook, whereas statistical heterogeneity was assessed using chi-square tests and I2 statistics. Review Manager 5.3 was used for statistical analysis. RESULTS: Ten randomized controlled trials with 488 patients who underwent NPWT or non-NPWT were included. Compared with non-NPWT, NPWT yielded an improved the percentage of graft take, a reduction in days from grafting to discharge, with lower relative risk of re-operation, and no increased relative risk of adverse event. Further, the subgroup analysis showed an improved the percentage of graft take in negative pressure of 80 mmHg, and no improved the percentage of graft take in negative pressure of 125 mmHg. CONCLUSION: NPWT is more effective than non-NPWT for the integration of skin grafts, and the negative pressure of 80 mmHg can be recommended. Data on adverse events and negative pressure are, however, limited. A better understanding of complications after NPWT and the ideal negative pressure for the integration of skin grafts is imperative.

Efficacy and Safety of Intralesional Triamcinolone Versus Combination of Triamcinolone with 5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis.

BACKGROUND: Although keloids and hypertrophic scars are common benign hyperproliferative growths of dermal fibroblasts, the clinical problems including physical and psychological problems are significant and impairing, with few proven treatments. Intralesional triamcinolone acetonide (TAC) and combination of TAC with 5-fluorouracil (5-FU) are widely used to treat keloids and hypertrophic scars, but their efficacy and safety remain controversial. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and CNKI for relevant trials. RESULTS: The mean scar height and the erythema score in the TAC + 5-FU group were lower than those in the TAC group after treatment (P < 0.05). The effectiveness based on observer assessment after treatment in the TAC + 5-FU group was superior than that in the TAC group (P < 0.05); further, the subgroup analysis showed the TAC + 5-FU group was also superior than the TAC group in the treatment of hypertrophic scars (P = 0.01), and there were no significant differences in the treatment of keloid (P = 0.12). The effectiveness based on patient self-assessment after treatment in the TAC + 5-FU group was also superior than the TAC group (P < 0.05). The overall complication rate in the TAC + 5-FU group was lower than the TAC group (P < 0.05). CONCLUSIONS: Combination of TAC with 5-FU is more effective and safer than TAC alone therapy in the treatment of keloids and hypertrophic scars. Data on keloids alone or hypertrophic scars alone are, however, limited. A better understanding of effective after intralesional combination of TAC with 5-FU in the treatment of keloids alone or hypertrophic scars alone is imperative. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A case report of a woman after childbirth with a dehisced abdominal wound as well as fat liquefaction and large skin necrosis.

Recently high-frequency electric knife and abdominal binder are widely used in the abdominal operation in China. Nevertheless, with the high occurrence of the abdominal wound, we think that whether both these operations could be used or not. Here, we report the case of a 40-year-old female patient where negative pressure wound therapy (NPWT) was applied to her dehisced abdominal wound as well as fat liquefaction and large skin necrosis with pleasing results. The patient with high fever was referred to our department from her earlier hospital for 6 days after cesarean delivery. During the surgery, her earlier doctor used a high-frequency electric knife for convenient-using, and after the operation, the patient immediately used an abdominal binder for good shape. However, the abdominal surgical incision was opened at postoperative day 3, with fat liquefaction releasing large fatty acids along both abdominal sides with penetration under the abdominal binder. After admitted at postoperative day 6 with aggravating wound, surgery was considered because of no reduction in the size of the wound. A series of vacuum sealing drainage (VSD) or vacuum-assisted closure (VAC) as well as others, were operated. In the admitted 25th day, the wound was completely closed. NPWT is a practical and effective therapy for the treatment of numerous refractory and intractable wounds. Therefore, we suggest that the high-frequency electric knife and an abdominal binder should be avoided using an abdominal operation. This case is the first report of the use of NPWT over a dehisced abdominal wound with fat liquefaction and large skin necrosis on a postpartum patient in China.

The Safety and Efficacy of Intralesional Verapamil Versus Intralesional Triamcinolone Acetonide for Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis.

BACKGROUND: Keloids and hypertrophic scars often result after skin trauma. Currently, intralesional triamcinolone acetonide (TAC) is the criterion standard in nonsurgical management of keloids and hypertrophic scars. Intralesional verapamil may be an effective alternative modality, but it has been insufficiently studied. Accordingly, the study authors conducted a systematic review and meta-analysis of randomized controlled trials to compare the efficacy and safety of the two drugs. METHODS: The study authors systematically searched the MEDLINE, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases for relevant trials published in any language through September 2018. RESULTS: According to the four studies included in this review, TAC improved scar pliability and vascularity more than verapamil after 3 weeks (P < .05). For scar height and scar pigmentation, no statistical difference was observed between the treatments (P > .05). The difference in effects on symptoms was not statistically significant (P = .89). For pain and telangiectasia, no statistical difference was observed (P > .05). Verapamil resulted in fewer cases of skin atrophy (P < .05). CONCLUSIONS: It appears that TAC is more effective than verapamil for improving scar pliability and vascularity in keloids and hypertrophic scars after 3 weeks of treatment. However, verapamil has fewer adverse drug reactions than TAC, which allows for a longer treatment period and the possibility that it might be effective for patients who cannot receive TAC.

Dual layered wound dressing with simultaneous temperature & antibacterial regulation properties.

Scald first-aid needs to reduce the local temperature as well as the bacterial colonization. Bacteria resistant problem has become a major challenge that global public health workers face. Long-term and high dosage use of antibacterial agents is the main reason. In this study, temperature-regulated release antibacterial nanoparticles were applied to poly(n-isopropyl acrylamide) and sodium polyacrylate. This hypothermia coverage could be used as an ideal scald first-aid wound dressing with spontaneous Temperature & Antibacterial regulation properties.

Experimental study of epidermal growth factor and acidic fibroblast growth factor in the treatment of diabetic foot wounds.

The aim of the present study was to investigate the effect of epidermal growth factor (EGF) and acidic fibroblast growth factor (aFGF) on the healing of diabetic foot wounds. A total of 199 patients with diabetic foot ulcers were recruited and randomly divided into four groups: A recombinant human EGF group (n=50), an aFGF group (n=50), a combined EGF and aFGF group (n=50) and a normal saline control group (n=49). Patients in all groups received a daily dressing change and growth factor reagents were applied topically when dressing. To observe the time required for each stage of wound healing, the epidermal healing rate and granulation tissue growth were recorded. Following 3-4 days of treatment, the wound healing stage was similar in all groups. Later stages (following 4 days) of wound healing were achieved significantly faster in the combined group compared with the control group (P<0.05). The rate of wound healing in the EGF group was similar to that observed in the combination group. No significant difference was observed between the EGF and aFGF groups during the initial period of wound healing. However, in the later stage (following 4 days), the combined use of recombinant human EGF and aFGF had a marked positive effect on wound healing when compared with the control group. Growth factors have extensive biological activities with functions including promoting cell proliferation as well as rehabilitating and regenerating tissues, which serve important roles in wound healing.

Lanthanum Chloride Inhibits LPS Mediated Expressions of Pro-Inflammatory Cytokines and Adhesion Molecules in HUVECs: Involvement of NF-κB-Jmjd3 Signaling.

BACKGROUND/AIMS: To investigate the regulation of LaCl3 on lipopolysaccharides (LPS)-induced pro-inflammatory cytokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs). METHODS: Primary cultured HUVECs were pretreated with 2.5 µM LaCl3 for 30 min followed by 1 µg/ml LPS for 2 h. Pro-inflammatory cytokine and adhesion molecule expressions were determined by real-time RT-PCR and ELISA. NF-κB/p65 nuclear translocation was examined by immunofluorescence and immuno-blot, and its DNA-binding activity was measured by chemiluminescence. Recruitment of NF-κB/p65, Jmjd3, and H3K27me3 to gene promoter regions was determined by ChIP-qPCR. RESULTS: LaCl3 exhibited no cytotoxic effects to primary HUVECs at concentrations ≤ 50 µM. LPS-mediated TNF-α, IL-1ß, IL-6, MMP-9, and ICAM-1 production, nuclear translocation, and DNA-binding activity of NF-κB/p65, as well as Jmjd3 expression, were all reduced significantly by LaCl3. Furthermore, LaCl3 treatment significantly impaired LPS-induced enrichment of NF-κB/p65 to the promoter regions of TNF-α, MMP-9, IL-1ß, ICAM-1, and IL-6; and of Jmjd3 to the promoter regions of TNF-α, MMP-9, IL-1ß, and IL-6. H3K27me3 abundance in the promoter regions of TNF-α and ICAM-1 increased significantly in following LaCl3 treatment. CONCLUSION: LaCl3 inhibits pro-inflammatory cytokine and adhesion molecule expressions induced by LPS in HUVECs. NF-κB and histone demethylase Jmjd3 are involved in this effect.

The regulation of Jmjd3 upon the expression of NF-κB downstream inflammatory genes in LPS activated vascular endothelial cells.

Inflammatory mediators and adhesion molecules have been implicated in a variety of diseases including atherosclerosis. As both the mediator-releasing and targeted cells, vascular endothelial cells play key role in pathological processes. NF-κB signaling regulates a cluster of inflammatory factors in LPS-activated vascular endothelial cells but the underlying mechanisms remain largely unknown. Here, we investigated the epigenetic regulation of LPS upon the expression of inflammatory mediators and adhesion molecules. We found that LPS treatment promoted jmjd3 expression, enhanced Jmjd3 nuclear accumulation in human vascular endothelial cells. In addition, LPS enhanced the demethylation of H3K27me3, a specific substrate of Jmjd3. LPS treatment recruited Jmjd3 and NF-κB to the promoter region of target genes, suggesting Jmjd3 synergizes with NF-κB to activate the expression of target genes. We further found that Jmjd3 attenuated the methylation status in promoter region of target genes, culminating in target gene expression. Our findings unveil epigenetic regulations of LPS upon NF-κB pathway and identify Jmjd3 as a critical modulator of NF-κB pathway and potential therapeutic target for NF-κB related diseases including atherosclerosis.

[Advancement in the diagnosis and management of toxic epidermal necrolysis].

Toxic epidermal necrolysis (TEN) is a potentially life-threatening condition usually attributed to severe adverse drug reactions. The evolvement of TEN, including extensive epidermal sloughing, fluid and electrolyte imbalances, hypermetabolism, immune dysfunction, sepsis and organs failure, are very similar to that of extensive burn. There is no unified therapeutic regimen for TEN due to its unclear pathogenesis.This article reviews the recent progress in regard to TEN in etiology, pathogenesis, diagnosis, differential diagnosis, treatment, new standard diagnostic approach, primary care, and supportive treatment.

Analysis of the mechanism of drug resistance of VIM-2-type metallo-β-lactamase-producing Acineto- bacter baumannii isolated from burn patients and its homology / 中华烧伤杂志

<p><b>OBJECTIVE</b>To study the drug resistance of Acinetobacter baumannii (AB) producing VIM-2-type metallo-β-lactamase (MBL) isolated from burn patients of our ward against carbapenem antibiotics and its homology.</p><p><b>METHODS</b>A total of 400 strains of AB (identified) were isolated from sputum, urine, blood, pus, and wound drainage. of burn patients hospitalized in our ward from September 2011 to March 2014. Drug resistance of the 400 strains of AB to 15 antibiotics, including compound sulfamothoxazole, aztreonam, etc. , was tested using the automatic microorganism identifying and drug sensitivity analyzer. Among the carbapenems-resistant AB isolates, modified Hodge test was applied to screen carbapenemase-producing strains. The carbapenemase genes of the carbapenemase-producing strains, and the mobile genetic elements class I-integron (Intl1) gene and conserved sequence (CS) of carbapenemase-producing strains carrying blaVIM-2 gene were determined with PCR and DNA sequencing. For carbapenemase-producing strains carrying blaVIM-2 gene, synergism test with imipenem-ethylene diamine tetraacetic acid (EDTA) and enhancement test with imipenem-EDTA and ceftazidime-EDTA were used to verify the MBL-producing status. Drug resistance of the VIM-2-type MBL-producing AB strains was analyzed. For VIM-2-type MBL-producing AB strains, plasmid conjugation experiment was used to explore the transfer of plasmid; outer membrane protein (OMP) CarO gene was detected by PCR. For VIM-2-type MBL-producing AB strains carrying CarO gene, the protein content of CarO was analyzed with sodium dodecyl sulfate polyacrylamide gel electro- phoresis. The repetitive consensus sequence of Enterobacteriaceae genome PCR (ERIC-PCR) was carried out for gene typing of VIM-2-type MBL-producing AB strains to analyze their homology.</p><p><b>RESULTS</b>(1) The resistant rates of the 400 strains of AB against levofloxacin and compound sulfamethoxazole were low. A total of 381 carbapenems-resistant AB strains were screened, including 240 carbepenemase-producing strains. (2) Out of the 240 carbepenemase-producing strains, 18 strains were found to harbor the blaVIM-2 gene, accounting for 7.5%; 133 strains carried the blaTEM-1 gene, accounting for 55.42%; 195 strains carried the blaOXA23 gene, accounting for 81.25%; 188 strains carried the bla(armA) gene, accounting for 78.33%. (3) Eighteen carbepenemase-producing strains which carried the bla(VIM-2) gene were found to carry the Intl1 gene, showing the Intl1-VIM linkage. Simultaneously, Intl1 variable area CS showed diversity. (4) Eighteen carbepenemase-producing strains which carried the blaVIM-2 gene were verified to produce MBL. The resistant rates of the 18 strains of AB against compound sulfamethoxazole were the lowest, followed by levofloxacin and cefoperazone/sulbactam, and those against the other antibiotics were above 60.00%. (5) Through multiple joint tests, plasmid conjugation experiment positive transfer strain was not found in 18 VIM-2-type MBL-producing AB strains. (6) Nine out of the 18 VIM-2-type MBL-producing AB strains were found to carry CarO gene. The OMP CarO of VIM-2-type MBL-producing AB strains carrying CarO gene was lost or lowered in the protein content. (7) The 18 VIM-2-type MBL-producing AB strains were classified into 6 genotypes by the ERIC-PCR. There were respectively 6, 4, 3, and 1 stain (s) in genotypes A, B, C, and F, and there were 2 strains in genotypes D and E respectively.</p><p><b>CONCLUSIONS</b>The resistance mechanism of AB against carbapenems is mainly mediated by blaTEM-1, blaOXA-23, and bla(arma); meanwhile, VIM-2-type MBL-producing and lack or change in OMP CarO are attributable to carbapenems resistance of clinically isolated AB from burn wards, and the Intl1 gene may take a part in blaVIM-2 gene transmission.</p>

[Experimental study on xenogenic acellular dermal matrix incorporated with silver].

OBJECTIVE: To investigate the biological characteristics of xenogenic acellular dermal matrix( Xeno-ADM) incorporated with silver, and to observe its effect in grafting. METHODS: Xeno-ADM was prepared with 0. 25% trypsin and 0. 5% triton X-100 , and then it was immersed in 2 g/L silver nitrate solution to prepare xeno-ADM incorporated with silver. The bacterial inhibitory effect of two kinds of xeno-ADM on burn wound was determined, and the histological characteristic of the wounds was observed with optical microscope, transmission electron microscope and scanning electron microscope. The Ag+ content in the xeno-ADM incorporated with silver was measured with atomic absorption spectrometer. Twenty-seven rabbits with full-thickness skin defects on the back were randomly divided into three groups, i. e. split-thickness skin autograft only( group A, n = 9) , xeno-ADM with overlying split-thickness skin autograft( group B, n = 9) , xeno-ADM incorporated with silver with overlying split-thickness skin autograft ( group C, n = 9). The skin specimens from grafted area in each group were harvested at 2,4 and 6 post-operation weeks( POW) and examined under light microscope and transmission electron microscope. The condition of the graft, the contraction degree of the grafts and the historical changes in grafting area were observed at 2,4,6 POW. The survival rate of the grafts was calculated and the proliferative activity of the lymphocyte in each group was determined at 2 POW. RESULTS: 1. Compared with xeno-ADM, the anti-bacterial effect of xeno-ADM incorporated with silver was much better ( P < 0. 05). No epidermis was seen in both types of xenografts ,and the collagen fibers were even in size and arranged regularly, with no obvious degeneration, and the dermis was also devoid of cells and cellular components. The Ag + content in xeno-ADM incorporated with silver measured (2. 7+/-0. 7) mg/g. 2. The grafts in B and C groups presented similar color to that of normal skin at 6 POW, and it was smooth, with fine texture and no scarring. The collagen fibers was arranged regularly, and conjunction between epidermis and dermis, the structure of basal cell desmosome and semi-desmosome were well reconstructed. The grafts in A group was in dark red color, with obvious contraction, and easily broken. The contraction rate in A group at 2,4 and 6 POW were obviously higher than those in B and C groups( P < 0. 05), while no obvious difference was observed between B and C groups. ( P >0. 05). The overall survival rate of the grafts in C group at 2 POW was 91.7% , which was evidently higher than that in A (77.8%) and B (80. 6% ) groups. The lymphocyte proliferative activity exhibited no difference among A, B and C groups( P >0.05). CONCLUSION: The xeno-ADM incorporated with silver has good anti-bacterial effect. In addition, it preserves the basic tissue structure and integral collagen fiber scaffold, without cells to induce rejection, so that it can be used as an ideal dermal substitute.

[Respiratory support with high frequency jet ventilation in severely burned patients with inhalation injury during early postburn stage].

OBJECTIVE: To observe the effects of respiratory support with high frequency jet ventilation (HFJV) in severely burned patients with inhalation injury during early postburn stage. METHODS: Twenty severely burned patients with TBSA of 79.6 +/- 29.3% and inhalation injury were enrolled in the study. Nineteen cases received tracheostomy after admission and only one received nasal intubation. All the patients underwent HFJV to correct hypoxia. The changes in blood gas analysis, respiratory rate and pulse were recorded before and 11 days after the ventilation. RESULTS: Tracheostomy was performed on 2.7 +/- 2.4 postburn days (PBDs), and HFJV was given during 4.4 +/- 2.9 PBDs. PaO(2) was evidently higher during 1 - 3 days after HFJV than that before the ventilation (P < 0.01) and remained at high level for 1 week after HFJV. There was no change in PaCO(2), respiratory rate and pulse during the ventilation. CONCLUSION: HFJV was beneficial in improving oxygenation and without any obvious side effects during the early management of severely burned patients with inhalation injury. This might be an optimal respiratory support pattern.