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Transforming Growth Factor-Beta (TGF-β) signalling pathway is of paramount importance in the processes of wound healing, epidermal integrity maintenance and development of skin cancer. The objective of this research endeavour was to clarify the impact of gene mutations and variations in expression within TGF-β family on mechanisms of tissue repair, as well as to identify potential targets for therapeutic purposes in non-melanoma skin cancer (NMSC). The methods utilized in this study involved obtaining RNA-seq data from 224 NMSC patients and paired normal skin tissues from the PRJNA320473 and PRJEB27606 databases. The purpose of the differential gene expression analysis was to identify genes whose expression had changed significantly. In order to evaluate the effects and interrelationships of identified gene variants, structural analysis with AlphaFold and PDB data and network analysis with the STRING database were both utilized. Critical gene expression was externally validated through the utilization of the GEPIA database. Tumour tissues exhibited a notable upregulation of genes associated with the TGF-β pathway, specifically MMP1, MMP3, MMP9, EGF, COL3A1 and COL1A2, in comparison with normal tissues. As indicated by the central node status of these genes in the network analysis, they play a crucial role in the progression of NMSCs. The results of the structural analysis suggested that mutations might cause functional disruptions. External validation of the upregulation confirmed the expression trends and emphasized the biomarker potential of the upregulated genes. In conclusion, this research offered thorough examination of molecular modifications that occur in TGF-β family genes, which are linked to cutaneous wound healing and NMSC. The modified expression of the identified hub genes may represent innovative targets for therapeutic intervention.
Chronic wounds contribute to significant healthcare and economic burden worldwide. Wound assessment remains challenging given its complex and dynamic nature. The use of artificial intelligence (AI) and machine learning methods in wound analysis is promising. Explainable modelling can help its integration and acceptance in healthcare systems. We aim to develop an explainable AI model for analysing vascular wound images among an Asian population. Two thousand nine hundred and fifty-seven wound images from a vascular wound image registry from a tertiary institution in Singapore were utilized. The dataset was split into training, validation and test sets. Wound images were classified into four types (neuroischaemic ulcer [NIU], surgical site infections [SSI], venous leg ulcers [VLU], pressure ulcer [PU]), measured with automatic estimation of width, length and depth and segmented into 18 wound and peri-wound features. Data pre-processing was performed using oversampling and augmentation techniques. Convolutional and deep learning models were utilized for model development. The model was evaluated with accuracy, F1 score and receiver operating characteristic (ROC) curves. Explainability methods were used to interpret AI decision reasoning. A web browser application was developed to demonstrate results of the wound AI model with explainability. After development, the model was tested on additional 15 476 unlabelled images to evaluate effectiveness. After the development on the training and validation dataset, the model performance on unseen labelled images in the test set achieved an AUROC of 0.99 for wound classification with mean accuracy of 95.9%. For wound measurements, the model achieved AUROC of 0.97 with mean accuracy of 85.0% for depth classification, and AUROC of 0.92 with mean accuracy of 87.1% for width and length determination. For wound segmentation, an AUROC of 0.95 and mean accuracy of 87.8% was achieved. Testing on unlabelled images, the model confidence score for wound classification was 82.8% with an explainability score of 60.6%. Confidence score was 87.6% for depth classification with 68.0% explainability score, while width and length measurement obtained 93.0% accuracy score with 76.6% explainability. Confidence score for wound segmentation was 83.9%, while explainability was 72.1%. Using explainable AI models, we have developed an algorithm and application for analysis of vascular wound images from an Asian population with accuracy and explainability. With further development, it can be utilized as a clinical decision support system and integrated into existing healthcare electronic systems.
This overview of systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically collate, appraise and synthesize evidence for the treatment of diabetic foot ulcers (DFUs) with the external application of Chinese herbal medicine (CHM). SRs/MAs of external application of CHM for DFUs were collected by searching Cochrane Library, Web of science, CNKI, PubMed, VIP, Embase and Wanfang. Two independent reviewers carried out the literature selection and data extraction. Subsequently, AMSTAR-2 tool, PRISMA, and GRADE system were applied by two reviewers independently to evaluate the methodological quality, reporting quality, and evidence quality of the included studies, respectively. Eight SRs/MAs met the eligibility criteria and were included. According to AMSTAR-2, a very low methodological quality assessment was given to the included SRs/MAs due to the flaws of items 2, 4 and 7. The PRISMA system identified protocol and registration weaknesses, as well as search method weaknesses. With GRADE, no high-quality evidence was identified to support the role of external application of CHM for DFUs, and the quality of evidence for the vast majority of outcomes was rated as low or moderate. In conclusion, low- to moderate-quality evidence supports the promise of external application of CHM for the treatment of DFUs. Due to the limitations of the evidence supporting external application of CHM for DFUs, rigorously designed and larger samples of high-quality studies are needed going forward before broad recommendations can be made.
This study focused on unravelling the role of PCAT-1 in wound-healing process, particularly its impact on regenerative and osteogenic abilities of mesenchymal stem cells (MSCs). We delved into how PCAT-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) and interacts with pivotal molecular pathways, especially β-catenin and PKM2, using human bone marrow-derived MSCs. MSCs were cultured under specific conditions and PCAT-1 expression was modified through transfection. We thoroughly assessed several critical parameters: MSC proliferation, mitochondrial functionality, ATP production and expression of wound healing and osteogenic differentiation markers. Further, we evaluated alkaline phosphatase (ALP) activity and mineral deposition, essential for bone healing. Our findings revealed that overexpressing PCAT-1 significantly reduced MSC proliferation, hampered mitochondrial performance and lowered ATP levels, suggesting the clear inhibitory effect of PCAT-1 on these vital wound-healing processes. Additionally, PCAT-1 overexpression notably decreased ALP activity and calcium accumulation in MSCs, crucial for effective bone regeneration. This overexpression also led to the reduction in osteogenic marker expression, indicating suppression of osteogenic differentiation, essential in wound-healing scenarios. Moreover, our study uncovered a direct interaction between PCAT-1 and the PKM2/β-catenin pathway, where PCAT-1 overexpression intensified PKM2 activity while inhibiting β-catenin, thereby adversely affecting osteogenesis. This research thus highlights PCAT-1's significant role in impairing wound healing, offering insights into the molecular mechanisms that may guide future therapeutic strategies for enhancing wound repair and bone regeneration.
This study was designed to identify risk factors for wound complications including surgical site infection (SSI) and wound healing issues following open reduction and internal fixation (ORIF) of ankle fractures. A retrospective analysis of individuals with ankle fractures treated with ORIF was undertaken. Study subjects were divided into a wound complications (WC) group and a no wound complication (NWC) group. The WC group was further divided into an SSI group and wound healing issues group. Twenty-one potential risk factors associated with wound complications after ORIF were tracked. Uni- and multivariate binary logistical regression analyses were used to identify risk factors associated with wound complications, ISS and wound healing issues. In total, 613 individuals, who had undergone surgery for ankle fractures formed the study cohort. The incidence of postoperative wound complications was 10.3% (63 cases), including 5.2% of SSI (32 cases) and 5.1% of wound healing issues (31 cases). The independent risk factors for wound complications were age 65 years or older, preoperative serum albumin level below 35 g/L, peripheral neuropathy, open fracture, fewer than seven cases per year in surgical volume, and attending surgeon level. The independent risk factors for SSI were age 65 years or older, preoperative serum albumin level below 35 g/L, open fracture and fewer than seven cases per year in surgical volume. The independent risk factors for wound healing issues were preoperative serum albumin level below 35 g/L, peripheral neuropathy, open fracture and attending surgeon level. Herein we found both factors inherent to the injury and individual and those pertaining to the surgical team affected the frequency of wound complications after ORIF of ankle fractures. Specifically, advanced age and low surgical volume were associated with a greater risk of SSI. Peripheral neuropathy and the low expertise level on the part of the surgeon were associated with a greater risk of wound healing issues. Hypoproteinaemia and open fracture were both associated with a greater risk of both SSI and wound healing issues.
Diabetic foot ulcer often leads to amputation, and both nutritional status and immune function have been associated with this process. We aimed to investigate the risk factors of diabetic ulcer-related amputation including the Controlling Nutritional Status score and neutrophil-to-lymphocyte ratio biomarker. We evaluated data from hospital in patients with diabetic foot ulcer, performing univariate and multivariate analyses to screen for high-risk factors and Kaplan–Meier analysis to correlate high-risk factors with amputation-free survival. Overall, 389 patients underwent 247 amputations over the follow-up period. After correction to relevant variables, we identified five independent risk factors for diabetic ulcer-related amputation: ulcer severity, ulcer site, peripheral arterial disease, neutrophil-to-lymphocyte ratio and nutritional status. Amputation-free survival was lower for the moderate-to-severe versus mild cases, for the plantar forefoot versus hindfoot location, for the concomitant peripheral artery disease versus without and in the high versus low neutrophil-to-lymphocyte ratio (all p < 0.01). The results showed that ulcer severity (p < 0.01), ulcer site (p < 0.01), peripheral artery disease (p < 0.01), neutrophil-to-lymphocyte ratio (p < 0.01) and Controlling Nutritional Status score (p < 0.05) were independent risk factors for amputation in diabetic foot ulcer patients and have predictive values for diabetic foot ulcer progression to amputation.
Among the assortment of available dressings aimed at promoting wound healing, moist dressings have gained significant popularity because of their ability to create an optimal environment for wound recovery. This meta-analysis seeks to compare the effects of moist dressing versus gauze dressing on wound healing time. A comprehensive literature search was conducted, encompassing publications up until April 1, 2023, across multiple databases including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Cochrane Library. Stringent criteria were used to determine study inclusion and evaluate methodological quality. Statistical analyses were performed utilizing Stata 17.0. A total of 13 articles, encompassing 866 participants, were included in the analysis. The findings indicate that moist dressing surpasses gauze dressing in terms of wound healing time (standard mean difference [SMD] −2.50, 95% confidence interval [CI] −3.35 to −1.66, p < 0.01; I 2 = 97.24%), wound site infection rate (odds ratio [OR] 0.30, 95% CI 0.17 to 0.54, p < 0.01; I 2 = 39.91%), dressing change times (SMD −3.65, 95% CI −5.34 to −1.97, p < 0.01; I 2 = 96.48%), and cost (SMD −2.66, 95% CI −4.24 to −1.09, p < 0.01; I 2 = 94.90%). Subgroup analyses revealed possible variations in wound healing time based on wound types and regions. This study underscores the significant advantages associated with the use of moist dressings, including expedited wound healing, reduced infection rates, decreased frequency of dressing changes, and lower overall treatment costs.
A novel autologous heterogeneous skin construct (AHSC) was previously shown to be effective versus standard of care (SOC) treatment in facilitating complete wound healing of Wagner 1 diabetic foot ulcers in an interim analysis of 50 patients previously published. We now report the final analysis of 100 patients (50 per group), which further supports the interim analysis findings. Forty-five subjects in the AHSC treatment group received only one application of the autologous heterogeneous skin construct, and five received two applications. For the primary endpoint at 12 weeks, there were significantly more diabetic wounds closed in the AHSC treatment group (35/50, 70%) than in the SOC control group (17/50, 34%) (p = 0.00032). A significant difference in percentage area reduction between groups was also demonstrated over 8 weeks (p = 0.009). Forty-nine subjects experienced 148 adverse events: 66 occurred in 21 subjects (42%) in the AHSC treatment group versus 82 in 28 SOC control group subjects (56.0%). Eight subjects were withdrawn due to serious adverse events. Autologous heterogeneous skin construct was shown to be an effective adjunctive therapy for healing Wagner 1 diabetic foot ulcers.
Proximal humerus fractures are common in clinical practice, and there are relatively a few studies on postoperative incision infections of such fractures. The purpose of this study was to explore the risk factors for surgical site infection (SSI) after internal fixation in patients with closed proximal humerus fractures. Patients with closed proximal humerus fractures who underwent surgery from January 2016 to January 2022 were retrospectively analysed. Cases with superficial or deep infections within 3 months after surgery were in the infection group and the remaining cases were in the non-infection group. The types of pathogenic bacteria in the infection group were analysed. The potential risk factors for SSI in all patients were recorded: (1) patient-related factors: gender, age, body mass index (BMI), smoking, comorbidities; (2) trauma-related factors: mechanism of injury, Injury Severity Score, visual analogue scale, fracture type, soft tissue condition and combined dislocation; (3) laboratory-related indexes: haemoglobin, albumin; (4) surgery-related factors: time from injury to surgery, American Society of Anesthesiologists anaesthesia classification, surgical time, fixation mode, intraoperative blood loss, suture method, bone graft and postoperative drainage. The risk factors for the occurrence of SSI were analysed using univariate analysis and multivariate logistic regression. The incidence of SSI was 15.7%. The most common bacterium in the infection group was Staphylococcus aureus. High BMI (p = 0.033), smoking (p = 0.030), an increase in mean time from injury to definitive surgery (p = 0.013), and prolonged surgical time (p = 0.044) were independent risk factors for the development of SSI after closed proximal humeral fractures. In patients with closed proximal humerus fractures, weight loss, perioperative smoking cessation, avoidance of delayed surgery, and shorter surgical time may be beneficial in reducing the incidence of SSI.
Pressure ulcers (PUs) are a common complication in postoperative patients with traumatic brain injury, and this study used a meta-analysis to assess the effects of comprehensive nursing applied in PUs intervention in postoperative patients with traumatic brain injury. A computerised systematic search of the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (CBM), VIP and Wanfang databases was performed to collect publicly available articles on randomised controlled trials (RCTs) on the effects of comprehensive nursing interventions in postoperative patients with traumatic brain injury published up to August 2023. Two researchers independently completed the search and screening of the literature, extraction of data and quality assessment of the included literature based on the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Twenty-eight articles were finally included, for a cumulative count of 2641 patients, of which 1324 were in the intervention group and 1317 in the control group. The results of the meta-analysis showed that, compared with conventional nursing, comprehensive nursing intervention helped to reduce the incidence of PUs in postoperative patients with traumatic brain injury (5.14% vs. 19.67%, odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.16–0.29, p < 0.00001) and reduced the incidence of postoperative complications (7.87% vs. 25.84%, OR: 0.22, 95% CI: 0.11–0.43, p < 0.0001), while increasing patient satisfaction (96.67% vs. 75.33%, OR: 9.5, 95% CI: 3.63–24.88, p < 0.00001). This study concludes that a comprehensive nursing intervention applied to postoperative patients with traumatic brain injury can significantly reduce the incidence of PUs and postoperative complications as well as improve nursing satisfaction, and it is recommended for clinical promotion. However, due to the limitations of the studies' number and quality, more high-quality, large-sample RCTs are needed to further validate the conclusions of this study.
Currently, there are two methods of treating subtrochanteric femur fractures: intramedullary nailing and extramedullary plate fixation. However, it remains to be seen whether internal or external fixation is the primary treatment for subrotator femur fractures in adults. In this meta-analysis, we reviewed the effects of internal and external fixation on the treatment of subrotator and subrotator fractures. Until July 2023, the researchers have been researching the Cochrane Library, Embase, Web of Science and PubMed, with English as their only language. The aims of the study are as follows: (1) to assess the efficacy of internal and external fixation for the treatment of postoperative wound infections in adult patients with subrotator femur fractures; (2) to assess the efficacy of various types of internal fixation for the treatment of adult patients with subrotator femur fractures, including postoperative complications, infections, and operative time. Meta-analysis showed that there was no significant difference in the treatment of subrotator fracture with internal versus external fixation in terms of wound infections, intra-operative bleeding, length of incision, and operative time were not significantly different. Therefore, more research is needed to support these findings with a number of large, high-quality randomized studies.
The objective of this research is to evaluate the risk of postoperative infection and other risks associated with robotic radical hysterectomy (RRH) compared with laparoscopic radical hysterectomy (LRH). Recent studies on RRH versus LRH have not been conclusive for cervical carcinoma. Our group attempted to use meta-analyses to evaluate the effects of both RRH and LRH on postoperative outcomes in order to make sure that the best operative method was used to prevent wound infections. We looked up Cochrane Library and published databases for this research and found 594 findings. Articles were screened by title and abstract and then carefully examined for inclusion and exclusion criteria. Data extraction was performed independently by two researchers. Comparison studies were used to describe the incidence of wound complications after surgery. The publication bias was assessed using Egger regression correlation analysis. There were six trials eligible for inclusion, of which 491 RRH and 807 LRH. Depending on surgery for cervical carcinoma, it is true that there is a difference in the way that surgery affects the postoperative complications. Our analysis demonstrated that the use of robotic operation can decrease the amount of blood loss during operation as compared with routine laparoscopy (MD, −77.69; 95% CI, −132.08, −23.30; p = 0.005). However, there were no statistical differences in the incidence of postoperative wound infections (OR, 0.54; 95% CI, 0.25, 1.19; p = 0.13) and intraoperative operative time (MD, 13.01; 95% CI, −41.38, 67.41; p = 0.64) among the two procedures. There was no statistically significant difference between these two groups of patients with severe postoperative complications. Unlike other research, the findings of this meta-analysis are not consistent with the findings of the present study, which suggest that robotic operations cannot lower the rate of postoperative wound infections. However, because of the limitations and the retrospective character of the trials covered, these findings should be interpreted with care and more extensive research is required.
A meta-analysis research was implemented to appraise the perineal wound complications (PWCs) after vertical rectus abdominis myocutaneous (VRAM) flap and mesh closure (MC) following abdominoperineal surgery (AS) and pelvic exenteration (PE) of anal and rectal cancers. Inclusive literature research till April 2023 was done and 2008 interconnected researches were revised. Of the 20 picked researches, enclosed 2972 AS and PE of anal and rectal cancers persons were in the utilized researchers' starting point, 1216 of them were utilizing VRAM flap, and 1756 were primary closure (PC). Odds ratio (OR) and 95% confidence intervals (CIs) were utilized to appraise the consequence of VRAM flap in treating AS and PE of anal and rectal cancers by the dichotomous approach and a fixed or random model. VRAM flap had significantly lower PWCs (OR, 0.64; 95% CI, 0.42–0.98, p < 0.001), and major PWCs (OR, 0.50; 95% CI, 0.32–0.80, p = 0.004) compared to PC in AS and PE of anal and rectal cancers persons. However, VRAM flap and PC had no significant difference in minor PWCs (OR, 1; 95% CI, 0.54–1.85, p = 1.00) in AS and PE of anal and rectal cancer persons. VRAM flap had significantly lower PWCs, and major PWCs, however, no significant difference was found in minor PWCs compared to PC in AS and PE of anal and rectal cancers persons. However, caution needs to be taken when interacting with its values since there was a low sample size of most of the chosen research found for the comparisons in the meta-analysis.
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