Omental coating attenuates implant-induced foreign body reaction in rats.

The objective of this study is to clarify whether the omental coating can effectively attenuate foreign body reaction (FBR) induced by implanted materials. Male Sprague-Dawley rats were injected with polydextran particle slurry intraperitoneally to activate the omentum. 7 days later, polyether polyurethane sponge discs were implanted subcutaneously on each side of the rat's back as the foreign implants to induce FBR. The next day, omental transposition were performed. The disc on the left side of each rat's back was wrapped with omental flap (omental group); the disc on the right side was untreated (control group). All discs were removed 21 days after implantation and assessed by determining the components of the fibrovascular tissue (angiogenesis, inflammation, foreign body giant cells (FBGCs) aggregation and fibrogenesis). In implants in omental group, micro vessel density (MVD), Hemoglobin (Hb) content and VEGF levels (pro-angiogenic cytokine) were increased when compared with implants from control group. Inflammatory parameters (IL-1ß; macrophage accumulation-NAG activity; neutrophil accumulation- MPO levels) were decreased in implants after omental coating. Also, collagen deposition, fibrous capsule thickness, and FBGCs decreased in implants from omental group. However, intra-implant levels of TNF-α and TGF-ß1 were not different after omental coating. Our findings showed for the first time that the omental coating around the implants attenuate the adverse FBR, it may be critical in developing new strategies to control FBR and improve the function and performance of the implanted materials.

Circ_072697 knockdown promotes advanced glycation end products-induced cell proliferation and migration in HaCaT cells via miR-3150a-3p/KDM2A axis.

OBJECTIVE: Diabetes foot ulcer (DFU) is a serious complication of diabetes, which can lead to significant mortality and amputation rate. Our previous study found circ_072697 was highly expressed in DFU tissues, but the regulatory mechanism of circ_072697 in DFU remains unclear. METHODS: The relative expressions of circ_072697, miR-3150a-3p, and KDM2A in DFU patients or advanced glycation end products (AGEs)-treated HaCaT cells (used as DFU cell model) were determined by using qRT-PCR. Cell proliferation and migration abilities were determined by using CCK-8 and Transwell assays. The interaction between miR-3150a-3p with circ_072697 or KDM2A were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. Furthermore, the protein expression of genes involved in MAPK signaling pathway was detected by western blot. RESULTS: The expression of circ_072697 was significantly upregulated in DFU tissues, while the expression of miR-3150a-3p was downregulated. Circ_072697 knockdown promoted the proliferation and migration of AGEs-treated HaCaT cells. miR-3150a-3p was confirmed as a target of circ_072697 and its inhibitor reversed the promotion effects of circ_072697 knockdown on biological behavior of cells. In addition, KDM2A was considered as a target of miR-3150a-3p and it was highly expressed in DFU samples. Importantly, circ_072697 could regulate KDM2A expression through sponging miR-3150a-3p, and this axis had effect on the MAPK signaling pathway. CONCLUSIONS: Overall, circ_072697 regulated the biological behaviors of keratinocytes in DFU via miR-3150a-3p/KDM2A axis and MAPK signaling pathway, revealing a new insight into the pathogenesis and potential therapeutic targets of DFU.

The burden of skin and subcutaneous diseases: findings from the global burden of disease study 2019.

Background: The small number of existing integrative studies on the global distribution and burden of all types of skin and subcutaneous diseases hinders relevant comparisons. Objective: This study aimed to determine the latest distribution, epidemiological differences, and factors potentially influencing each skin and subcutaneous disease and the policy implications. Methods: Data on the skin and subcutaneous diseases were obtained from the Global Burden of Disease Study 2019. The incidence, disability-adjusted life years (DALYs), and deaths due to skin and subcutaneous diseases in 204 countries and regions from 1990 to 2019 were analyzed and stratified by sex, age, geographical location, and sociodemographic index (SDI). The annual age-standardized rate of change in the incidence was obtained to evaluate temporal trends. Results: Of 4,859,267,654 (95% uncertainty interval [UI], 4,680,693,440-5,060,498,767) new skin and subcutaneous disease cases that were identified, most were fungal (34.0%) and bacterial (23.0%) skin diseases, which accounted for 98,522 (95% UI 75,116-123,949) deaths. The burden of skin and subcutaneous diseases measured in DALYs was 42,883,695.48 (95%UI, 28,626,691.71-63,438,210.22) in 2019, 5.26% of which were years of life lost, and 94.74% of which were years lived with disability. The highest number of new cases and deaths from skin and subcutaneous diseases was in South Asia. Globally, most new cases were in the 0-4-year age group, with skin and subcutaneous disease incidence slightly higher in men than in women. Conclusion: Fungal infections are major contributors to skin and subcutaneous diseases worldwide. Low-middle SDI states had the highest burden of skin and subcutaneous diseases, and this burden has increased globally. Targeted and effective management strategies based on the distribution characteristics of each country are, thus, required to reduce the burden of skin and subcutaneous diseases.

Single-cell analysis reveals melanocytes may promote inflammation in chronic wounds through cathepsin G.

During acute wound (AW) healing, a series of proper communications will occur between different epidermal cells at precise temporal stages to restore the integrity of the skin. However, it is still unclear what variation happened in epidermal cell interaction in the chronic wound environment. To provide new insights into chronic wound healing, we reconstructed the variations in the epidermal cell-cell communication network that occur in chronic wound healing via single-cell RNA-seq (scRNA-seq) data analysis. We found that the intricate cellular and molecular interactions increased in pressure ulcer (PU) compared to AW, especially the PARs signaling pathways were significantly upregulated. It shows that the PARs signaling pathways' main source was melanocytes and the CTSG-F2RL1 ligand-receptor pairs were its main contributor. Cathepsin G (CatG or CTSG) is a serine protease mainly with trypsin- and chymotrypsin-like specificity. It is synthesized and secreted by some immune or non-immune cells. Whereas, it has not been reported that melanocytes can synthesize and secrete the CTSG. F2R Like Trypsin Receptor 1 (F2RL1) is a member of proteinase-activated receptors (PARs) that are irreversibly activated by proteolytic cleavage and its stimulation can promote inflammation and inflammatory cell infiltration. In this study, we found that melanocytes increased in pressure ulcers, melanocytes can synthesize and secrete the CTSG and may promote inflammation in chronic wounds through CTSG-F2RL1 pairs, which may be a novel potential target and a therapeutic strategy in the treatment of chronic wounds.

The epidemiological characteristic and trends of burns globally.

BACKGROUND: Burns is a type of injury, caused by unintentional exposure to substances of high temperature, including hot liquid, solid, and objects radiating heat energy, placing a high burden not only on patients' families but also on national healthcare systems globally. It is difficult for policymakers and clinicians to formulate targeted management strategies for burns because data on current epidemiological patterns worldwide are lacking. METHODS: Data on burns were obtained from the Global Burden of Disease (GBD) 2019 Study. The incidence, disability-adjusted life years (DALYs), and deaths of burns in 204 countries and regions from 1990 to 2019 were calculated and stratified by sex, age, geographical location, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) of incidence, DALYs, and deaths was calculated to evaluate the temporal trends. All analyses were performed using R software, version 4.1.1, with 2-sided P-values < .05 indicating a statistically significant difference. RESULTS: A total of 8,378,122 new cases (95% UI, 6,531,887-10,363,109cases) of burns were identified globally in 2019, which is almost evenly split between men and women, and most of the new cases were concentrated in the 10-19-year age group. Besides, burns account for 111,292 deaths (95% UI, 132,392-88,188) globally in 2019, most of which were concentrated in those aged 1-4 years. The burden of burns measured in DALYs was 7,460,448.65 (95% UI, 5,794,505.89-9,478,717.81) in 2019, of which 67% and 33% could be attributed to YLLs and YLDs, respectively. The EAPC of incidence, DALYs, and deaths were negative, the age-standardized rate (ASR) of incidence, DALYs, and deaths were considered to be decreasing in most of the regions, and the EAPCs were negatively correlated with SDI levels, universal health coverage (UHC), and gross domestic product (GDP). CONCLUSION: Globally, the age-standardized rates of burn incidence, DALYs, and mortality, as well as the number of burn DALYs and death cases will continuously decrease, but the number of new burn cases has an increasing tendency globally. In addition, the EAPCs of burns in incidence, DALYs, and deaths indicated that the burden of burns was considered to be decreasing in most of the regions. And from the relationship of EAPCs with SDI, UHC index, and GDP, indicate that prevention burns not only depend on health spending per capita but also depend on the education level per capita and healthcare system performance, but it does not mean higher health spending corresponds to higher UHC index, which needs high efficiency of translating health spending into individuals health gains.

Efficacy and safety of CO2 laser in the treatment of chronic wounds: A Retrospective Matched Cohort Trial.

OBJECTIVES: Treating chronic cutaneous wounds is challenging, and debridement is a central concept in treating them. Studies have shown that CO2 laser debridement can control local infection and promote the wound healing process. The present study aimed to investigate the efficacy and safety of fully ablative CO2 laser debridement compared to routine surgical debridement in the treatment of chronic wounds. METHODS: The retrospective cohort study was conducted on patients with chronic (>1 month) cutaneous wounds (≥1 cm2 ) between December 1, 2017, and December 1, 2020, in the Wound Healing Center at Shanghai Ruijin Hospital, China. Patients treated with CO2 laser debridement with a DEKA SmartXide2 C80 (DEKA) (the CO2 laser group) were compared with matched control patients with similar baseline characteristics who had undergone routine surgical debridement (the routine group). The primary outcome was time-to-heal (days) for chronic wounds in two groups, and secondary outcomes included the wound area and BWAT (Bates-Jensen wound assessment tool) score before treatment, and at 1, 2, 3, and 4 weeks after treatment. RESULTS: The study included 164 patients (82 in the CO2 laser group and 82 matched in the routine group). The time-to-heal for patients in the CO2 laser group (41.30 ± 17.11) was significantly shorter than that of the patients in the routine group (48.51 ± 24.32) (p = 0.015). At 3 and 4 weeks after treatment, the absolute wound area of the CO2 laser group was significantly smaller than that of the routine group. Also, the CO2 laser group exhibited a significantly lower relative area at 2, 3, and 4 weeks after treatment. The CO2 laser group yielded significantly lower BWAT scores at 2, 3, and 4 weeks after treatment. Additionally, the relative BWAT score was significantly lower in the CO2 laser group than the relative scores in the routine group at 2, 3, and 4 weeks after treatment. No adverse events related to the treatments were observed in either group during the study period. CONCLUSIONS: The present study has shown that fully ablative CO2 laser debridement has several advantages over routine sharp surgical debridement. It is superior at ameliorating wound status and reducing wound area, and it also significantly reduces the time-to-heal for chronic wounds, without causing any adverse events.

Application of Compound Polymyxin B Ointment in the Treatment of Chronic Refractory Wounds.

The purpose of this study was to investigate the clinical efficacy of compound polymyxin B ointment for treating chronic refractory wounds. A retrospective analysis was performed on 111 patients who underwent chronic refractory wound treatment. Patients were divided into 2 groups, with 45 patients included in the experimental group (compound polymyxin B group) and 66 patients included in the control group (silver sulfadiazine group). After thorough debridement in both groups, either compound polymyxin B ointment or silver sulfadiazine cream was evenly applied to the patient's wound and covered with sterile gauze. In both groups, dressing changes were dependent on the wound's condition and secretions. Using the Bates-Jensen Wound Assessment Tool (BWAT), patients in both groups were scored, after which wound healing, infection, and healing time were compared. There was no significant difference in BWAT scores between the 2 groups on the 7th or 14th day; however, on the 21st day, the BWAT score in the experimental group was significantly lower than that of the control group. The difference was statistically significant (P < .05). There was no significant difference in the BWAT-I scores between the 2 groups on the seventh day. The healing time in the experimental group was significantly shorter than that of the control group, and the difference was statistically significant (P < .05). For the treatment of chronic refractory wounds, thorough debridement followed by compound polymyxin B ointment topical application can reduce and control wound infection effectively and accelerate the process of wound repair.

Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to facilitate tissue repair in diabetic wounds.

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO-induced dysfunction. We observed that the accumulation of MGO-derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO-derived AGEs in the wound tissue of type-2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1-like macrophages induced by lipopolysaccharide (LPS), but not those of M0-like macrophages induced by PMA or of M2-like macrophages induced by interleukins 4 (IL-4) and 13 (IL-13); the impaired phagocytosis of M1-like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non-healing diabetic wounds.

Fractal analysis of rat dermal tissue in the different injury states.

Scar formation and chronic ulcers can develop following a skin injury. They are the result of the over- or underproduction of collagen. It is very important to evaluate the quality and quantity of the collagen that is produced during wound healing, especially with respect to its structure, as these factors are very important to a complicated outcome. However, there is no standard way to quantitatively analyse dermal collagen. As prior work characterised some potentially fractal properties of collagen, it was hypothesised that collagen structure could be evaluated with fractal dimension analysis. Small-angle X-ray scattering technology (SAXS) was used to evaluate the dermis of rats exposed to graft harvest, burn, and diabetic pathologic states. It was found that almost all collagen structures could be quantitatively measured with fractal dimension analysis. Further, there were significant differences in the three-dimensional (3-D) structure of normal collagen versus that measured in pathologic tissues. There was a significant difference in the 3-D structure of collagen at different stages of healing. The findings of this work suggest that fractal analysis is a good tool for wound healing analysis, and that quantitative collagen analysis is very useful for assessing the structure of dermal collagen.

Successful Postoperative Nephrocutaneous Fistula Treatment With Omental Flap Grafting: A Case Report.

Nephrocutaneous fistula (NCF) is a rare and severe complication of renal disease and surgical procedures. Treatments for NCF are based on the renal function, and can include nephrectomy, heminephrectomy, nephroureterectomy, endourological maneuvers or antibiotic therapy alone. Here we report a case of a chronic NCF which occurred 5 years after partial nephrectomy. In this report, we describe a new surgical approach for the management of a patient with postoperative NCF. In the present case, in addition to removing the fistulous tract, we also performed an omental flap grafting to tightly cover the kidney. In addition to limiting and controlling the local inflammation, the omental flap prevents contact between the kidney and the flank muscle on its posterior rim. No recurrence or complications occurred throughout 10 months of follow-up. The NCF was successfully treated with completely removal of the sinus tract and omental flap grafting, without nephrectomy. This case adds new aspects to the treatment of NCF.

Transient exposure to elevated glucose levels causes persistent changes in dermal microvascular endothelial cell responses to injury.

BACKGROUND: The purpose of this study was to determine whether elevated glucose can induce a dermal microvascular endothelial cell metabolic memory, thus affecting angiogenesis in the repair process of mammalian cutaneous wound. We hypothesized that transient elevated glucose levels cause sustained alteration of endothelial cell responses to injury and persistent epigenetic changes in gene expression. METHODS: Human dermal microvascular endothelial cells were exposed to experimental conditions with or without 30 mM D-glucose. The control group was maintained at 5 mM D-glucose; while in the transient glucose group, after being exposed to 30 mM D-glucose for two days, then being put under the control conditions during the experiment. Besides, in the whole process of the experiment, the chronic glucose group was kept in the condition with 30 mM D-glucose. Proliferation, migration, tube formation, gene expression and histone methylation were assessed for individual conditions. RESULTS: Transient elevated glucose caused sustained effects on endothelial cell migration, tube formation and TIMP3 gene expression. The effects on TIMP3 expression were associated with persistent changes in histone modification at the 5' end of the TIMP3 gene, suggesting an epigenetic effect. CONCLUSIONS: Hyperglycemia induced metabolic memory could promote the regulation of TIMP3, and it can be used as a possible innovative molecular target for therapeutic intervention in the treatment of chronic non-healing diabetic wounds.

Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves' disease (GD). Although fibroblast stimulated by thyroid-stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid-stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin-associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.

Distribution and Antibiotic Resistance Patterns of Pathogenic Bacteria in Patients With Chronic Cutaneous Wounds in China.

Background: To determine the distribution and antimicrobial susceptibility pattern of pathogenic bacteria in patients with chronic cutaneous wounds on a national scale. Methods: A retrospective study was conducted using the data recorded between January 1, 2018 and January1, 2020 in 195 hospitals across China. After screening the data, 815 patients with chronic wounds were finally analyzed. The data collected included information about the patients' general condition and local cutaneous wound assessments, especially microbial culture and antibiotic susceptibility tests. The analyses were performed using SPSS Version 26. Results: The study included 815 patients (290 [35.6%] females; 63 [50-74] years). The most common causes of chronic cutaneous wounds were diabetes (183, 22.5%), infection (178, 21.8%), and pressure (140, 17.2%). Among these, 521(63.9%) samples tested yielded microbial growth, including 70 (13.4%) polymicrobial infection and 451 (86.6%) monomicrobial infection. The positive rate of microbial culture was highest in wound tissue of ulcers caused by infection (87.6%), followed by pressure (77.1%), diabetes (68.3%), and venous diseases (67.7%). Bates-Jensen wound assessment tool (BWAT) scores >25 and wounds that lasted for more than 3 months had a higher positive rate of microbial culture. BWAT scores >25 and wounds in the rump, perineum, and feet were more likely to exhibit polymicrobial infection. A total of 600 strains were isolated, of which 46.2% (277 strains) were Gram-positive bacteria, 51.3% (308 strains) were Gram-negative bacteria, and 2.5% (15 strains) were fungi. The most common bacterial isolates were Staphylococcus aureus (29.2%), Escherichia coli (11.5%), Pseudomonas aeruginosa (11.0%), Proteus mirabilis (8.0%), and Klebsiella pneumoniae (5.8%). The susceptibility tests showed that 116 cultured bacteria were Multidrug resistant (MDR) strains. The resistance rates of S. aureus were 92.0% (161/175) to penicillin, 58.3% (102/175) to erythromycin, and 50.9% (89/175) to clindamycin. Vancomycin was the most effective antibiotic (0% resistance rate) against all Gram-positive bacteria. Besides, the resistance rates of E. coli were 68.1% (47/69) to ampicillin, 68.1% (47/69) to ciprofloxacin, 60.9% (42/69) to levofloxacin. However, all the isolated Gram-negative bacteria showed low resistance rates to tigecycline (3.9%) and amikacin (3.6%). Conclusions: The distribution of bacteria isolated from chronic cutaneous wounds varies with the BWAT scores, causes, duration, and the location of wounds. Multidrug resistance is a serious health issue, and therefore antibiotics used in chronic wounds must be under strict regulation. Our findings may help clinicians in making informed decisions regarding antibiotic therapy.

Different therapeutic effects between diabetic and non-diabetic adipose stem cells in diabetic wound healing.

OBJECTIVE: This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. METHOD: The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments. RESULTS: ASC density was decreased in diabetic rats. The generation time of ASC-rich cells from diabetic rats (d-ASC-rich cells) was longer than that of ASC-rich cells from non-diabetic rats. The number of pre-apoptotic cells in the third generation (passage 3) of d-ASC-rich cells was higher than that among the ASC-rich cells from non-diabetic rats. CD31 and CD34 expression was higher in d-ASC-rich cells than in ASC-rich cells from non-diabetic rats, whereas CD44 and CD105 expression was lower than that in ASC-rich cells from non-diabetic rats. Transplantation of ASC-rich cells from non-diabetic rats promoted wound healing in both non-diabetic and diabetic rats. In contrast, d-ASC-rich cells and enriched nuclear cells only promoted wound healing in non-diabetic rats. ASC-rich cell transplantation promoted greater tissue regeneration than d-ASC-rich cell transplantation. CONCLUSION: ASC-rich cells promoted wound healing in diabetic and non-diabetic rats. ASC density was lower in the adipose tissue of diabetic rats compared with non-diabetic rats. d-ASC-rich cells did not promote wound healing in diabetic rats, suggesting that caution is warranted regarding the clinical use of diabetic adipose stem cell transplantation for the treatment of diabetic wounds.

Effects of advanced glycation end products on neutrophil migration and aggregation in diabetic wounds.

Increased accumulation of advanced glycation end products (AGEs) in diabetic skin is closely related to delayed wound healing. Studies have shown that the concentration of AGEs is elevated in the skin tissues and not subcutaneous tissues in refractory diabetic wounds, which suggests there may be a causal relationship between the two. In the present study, in vitro experiments revealed that AGEs activated neutrophils, and the migratory and adhesive functions of neutrophils decreased once AGE levels reached a certain threshold. Different levels of AGE expression differentially affected the function of neutrophils. Messenger RNA (mRNA) sequencing analysis combined with real-time polymerase chain reaction (PCR) showed that poliovirus receptor (PVR/CD155) and CTNND1, which play a role in migration- and adhesion-related signaling pathways, were decreased following AGE stimulation. Consequently, neutrophils cannot effectively stimulate the formation of the inflammatory belt needed to remove necrotic tissues and defend against foreign microorganisms within diabetic chronic wounds. In addition, this phenomenon may be related to the differential accumulation of AGEs in different layers of the skin.

The effects and mechanism of Kangfuxin on improving healing quality and preventing recurrence of gastric ulcer.

This study investigated the gastroprotective effects and possible mechanism of Kangfuxin (KFX), an ethanol extract of Periplaneta americana L. (Dictyoptera; Blattidae), on improving healing quality and preventing recurrence of gastric ulcer. The effects of KFX were investigated in patients treated with endoscopic submucosal dissection (ESD), gastric ulcer animal model, and rat gastric mucosal cells and fibroblasts. Moreover, the relationship between KFX and p38/NF-κB pathway were explored both in vivo and in vitro. In patients, KFX exhibited protective effects against gastric ulcers and resulted in a decrease in the CD3 expression. In vivo animal experiments confirmed that KFX accelerated ulcer healing by promoting neovascularization (increased CD34 expression), suppressing inflammation (decreased interleukin-1ß (IL-1ß), myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and IL-8 expression), and enhancing growth factor expression, including the epidermal growth factor receptor (EGFR) and hepatocyte growth factor (HGF). In vitro experiments demonstrated that treatment with 10% KFX rat serum decreased IL-1ß, IL-1Ra, SIL-1RAP, TNF-α, and ICAM-1 expression in rat gastric mucosal cells or fibroblasts and increased IL-1R expression compared to that in the group treatment with 10% normal rat serum. Furthermore, KFX inhibited the activation of p38/NF-κB pathway both in vivo and in vitro. In conclusion, KFX treatment could effectively improve healing quality and prevent gastric ulcer recurrence, which might be attributed to neovascularization, suppressed inflammation, and enhanced growth factor expression. The p38/NF-κB pathway may be one of important mechanism to mediate the effects of KFX.

Identification of potential circRNAs and circRNA-miRNA-mRNA regulatory network in the development of diabetic foot ulcers by integrated bioinformatics analysis.

We aimed to explore the mechanism of circular RNAs (circRNAs) and provide potential biomarkers for molecular therapy of diabetic foot ulcers (DFU). Gene expression profile of GSE114248, including five normal samples and five DFU samples, was downloaded from GEO database. Differentially expressed circRNAs (DEcircRNAs) between two groups were identified. Then, DEcircRNA-miRNA and miRNA-mRNA interaction was revealed, followed by the circRNA-miRNA-mRNA network construction. Moreover, functional and pathway analysis were performed based on mRNAs, followed by the DM-related pathway exploration. Specific binding sites for key circRNAs and associated miRNAs were under investigation. Finally, RT-qPCR was used to verify the candidate the relative expression level of circRNA between normal tissues and DFU. Totally, 65 DEcircRNAs were revealed between two groups, followed by 113 circRNA-miRNA-mRNA interactions explored. The mRNAs in these interactions were mainly assembled in functions like cell proliferation and pathways. Moreover, a total of 11 DM-related pathways were revealed. Finally, circRNA-miRNA specific binding-site analysis revealed two key circRNAs, for example, circRNA_072697 and circRNA_405463, corresponding to their miRNAs. These two circRNAs were novel biomarkers for DFU. circRNA_072697 acted as a sponge of miR-3150a-3p in the progression of DFU via regulating KRAS. MAPK signaling pathway might contribute to the development of DFU.

Potential molecular mechanisms of negative pressure in promoting wound healing.

Negative pressure wound therapy (NPWT) has been widely used in various lesions. This study aimed to explore the biological effects of negative pressure on the polymorphonuclear neutrophils (PMNs), macrophages, and epidermal keratinocyte cells involved in wound healing. PMNs differentiated from HL-60, macrophages were derived from THP-1 monocytes, and keratinocytes were cultured in vitro, and they were treated with 0, -0.03 mp, and -0.05 mp, respectively. Cell ultrastructure; viability; apoptosis; and protein factors such as tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), interleukin-17 (IL-17), and cell division cycle 42 (Cdc42) were determined by transmission electron microscopy (TEM), CCK8, flow cytometry (FCM), ELISA, and simple Western assays, respectively. After negative pressure stimulation, the cell ultrastructure of PMNs and macrophages cells was presented with a marked increase of lysosomes and a relative decrease of mitochondria. In addition, the cell viability was enhanced in PMNs and macrophages in a pressure-dependent manner and apoptosis ratios were significantly reduced in PMNs and macrophages. In addition, under -0.05 negative pressure, IFN-γ and IL-17 were significantly increased in PMNs or macrophages. Moreover, increased EGF and EGFR and Cdc42 levels in keratinocytes induced by the -0.05 mpa were detected, indicating that the migration chemotaxis of keratinocyte cells was enhanced. Negative pressure might promote cell proliferation, accelerate inflammatory responses, and promote epithelialisation during wound healing by increasing IFN-γ, IL-17, Cdc42, EGF, and EGFR in PMNs, macrophages, or keratinocytes under different negative pressures.

Epidemiological investigation of vascular etiological examinations in the diagnosis and treatment of lower-extremity ulcers in China.

The vascular causes of lower-extremity ulcers cannot be neglected because they can directly affect treatment methods. No detailed epidemiological statistics have described vascular etiological diagnosis in China. This study aimed to explore the prevalence of clinical vascular etiological examination of lower-extremity ulcers and improve the diagnosis and treatment effectiveness of lower-extremity ulcers. Data were collected from the WoundCareLog database, which includes 2413 cases of lower-extremity ulcers from 478 hospitals nationwide. Data analysis revealed that 1698 (70.4%) lower-extremity blood flow examinations (including physical examination [PE] and assistant examinations [AE]) were performed, of which 61.7% were PE, 10.4% were AE only, and 27.9% were the combined PE and AE[PAE]. The proportion of nonexaminations was higher in the nondiabetic group than in the diabetic group (χ2 = 34.5; P < .01). The positive rates of vascular etiological examination in the diabetic and nondiabetic groups were 69.7% and 70.7%, respectively. Among the four economic regions of China, there were statistically significant differences in the use of the different examination methods. The examination of vascular diseases in lower-extremity ulcers in China has not been fully popularized and requires improvement; there was no statistically significant difference between examination rates by doctors and nurses, which is mainly based on PE. However, PE has certain rates of misdiagnosis and missed diagnosis. The false-positive and false-negative rates were 25.7% and 57.6%, respectively. The use of an AE can compensate for this deficiency by making diagnosis more precise, while the quantitative diagnostic criteria allow disease diagnosis to transcend geographical and operator differences and maximize uniformity. The vascular B-ultrasound examination is more suitable for the medical environment in China because of its mature technology, high hospital penetration rate, and low cost.

WoundCareLog APP - A new application to record wound diagnosis and healing.

The incidence of chronic wounds has been increasing over the past 20 years. However, the standardized diagnosis and treatment practice of chronic refractory wounds have not been established. In addition, the properties of the wound are characterized by morphology and thus correct description of the wound in medical history collection plays a vital role, which directly affects the definitive diagnosis. To develop more accurate format of clinical history record which can correctly reflect a patient's course and treatment progress, and to standardize the medical history record of chronic refractory wounds, at the national or regional level, we designed the WoundCareLog APP. It acts as a recording and communication tool for wound healing specialists at all levels of medical institutions in China. The WoundCareLog APP is fully compatible to meet the criteria and requirements of conventional medical records by embedding 9 modules. In addition, the demands for morphological description of wounds in wound healing diagnosis and treatment have been fulfilled by enroll of digital imaging technology to overcome the inadequacies of traditional medical history records.