Exploring Effect and Mechanism of Astragaloside on Repair and Healing in Chronic Non-healing Wound Rat Model Based on SIRT1 and PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the promotional effect of astragaloside on the repair and healing of chronic non-healing wounds and its mechanism. MethodA total of 60 male SD rats were constructed with full-layer skin defect wounds on the back， and except for the control （Con） group， the rest were constructed with non-healing wounds， which were then randomly divided into the sham-operation （sham） group， the low-dose astragaloside group， the high-dose astragaloside group， the astragaloside + LY294002 ［phosphatidylinositol 3-kinase （PI3K） inhibitor］ group， and the astragaloside + EX527 ［silencing regulatory protein 1 （SIRT1） inhibitor］ group. The percentage of wound area in each group was observed on the 2nd， 4th， 6th， and 8th days after wound molding. Collagen type Ⅰ alpha 1 （COL1A1） and alpha smooth muscle actin （α-SMA） expressions in the wound tissue were detected by immunofluorescence. Hematoxylin and eosin （HE） staining was performed to determine the pathological structure of the wound. The mRNA expression of inflammatory factors in the wound was measured by real-time polymerase chain reaction （Real-time PCR）， and the expression of proteins related to the SIRT1/ nuclear factor （NF）-κB and PI3K/protein kinase B （Akt） signaling pathways in the wound was tested by Western blot. ResultCompared with the sham group， the percentage of postoperative wound area of rats in both low-dose and high-dose astragaloside groups gradually decreased with time， and the efficacy of the high-dose astragaloside group was better. Compared with the Con group， the fluorescence intensity of COL1A1 in wound tissue of the sham group decreased， while the expression of α-SMA increased. The epithelial tissue was severely damaged， with an increase in the thickness， and a large number of inflammatory cells were seen in the infiltration. The mRNA expression of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and inducible nitric oxide synthase （iNOS） was elevated. The protein expression of NF-κB p65， p-PI3K/PI3K， and p-Akt/Akt was elevated， while SIRT1 expression was decreased （P<0.05）. Compared with the sham group， the fluorescence intensity of COL1A1 and α-SMA increased after astragaloside treatment. The number of epithelial cells increased， and the thickness decreased. The inflammatory cells decreased， and the amount of collagen increased. The mRNA expression of TNF-α， IL-1β， IL-6， and iNOS was decreased， and the protein expression of NF-κB p65， p-PI3K/PI3K， and p-Akt/Akt was decreased. SIRT1 was elevated， and the effect was better in the high-dose astragaloside group （P<0.05）. Compared with the high-dose astragaloside group， inhibition of the PI3K/Akt and SIRT1 pathways by LY294002 and EX527 prevented the therapeutic efficacy of astragaloside on chronic non-healing wounds. ConclusionThe topical application of astragaloside significantly promotes the healing of chronic non-healing wounds in rats， and the mechanism may be related to the activation of the PI3K/Akt pathway and the SIRT1/NF-κB pathway.

Plastic and reconstruction surgery for non-healing wound after posterior spinal surgery / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical significance of different plastic surgeries in the treatment of poor healing wound after posterior spinal internal fixation.@*METHODS@#In this study, 16 patients with poor incision healing after posterior spinal internal fixation were retrospectively included, and dif-ferent plastic surgery treatment plans were determined according to the wound characteristics and defect condition. The measures included debridement, vacuum sealing drainage (VSD), and different tissue flaps according to the location and extent of the defect.@*RESULTS@#A total of 16 patients meeting the criteria were included, of whom 3 were treated with debridement combined with VSD and wound suture directly, 6 were treated with debridement combined with Z-flap for wound repair, 1 was treated with bilateral sacrospinous muscle flap for dural defect repair combined with Z-flap for skin wound repair, 1 was treated with lectus dorsi flap for wound repair, 3 were treated with the fourth lumbar artery perforator flap for wound repair. The wound was repaired with local rotating flap in 1 case and gluteus maximus musculocutaneous flap in 1 case. Among the 16 patients, 7 cases were positive for wound culture, including 3 cases of Staphylococcus aureus, 1 case of Pseudomonas aeruginosa, 1 case of Staphylococcus epidermidis, 1 case of Escherichia coli, 1 case of Klebsiella pneumoniae, and the other 9 cases were negative. After surgery, there were 7 patients with different degrees of poor wound healing, including 3 patients undergoing dressing change, 2 patients undergoing secondary debridement and suture, 1 patient undergoing free scalp skin graft, and 1 patient undergoing local effusion suction treatment. All the above 7 patients were discharged from hospital after improvement, and the remaining 9 patients had good first-stage wound hea-ling after surgery. None of the 16 patients underwent internal fixation.@*CONCLUSION@#Multiple factors could lead to poor wound healing after posterior spinal internal fixation. Early intervention, thorough debridement, removal of necrotic/infected tissue, and selection of suitable skin flap for effective wound fil-ling and covering were important means to ensure wound healing after spinal surgery and reduce removal of internal fixation.

Role of vacuum assisted closure in wound healing among patients attending a tertiary care hospital

Background: Vacuum assisted closure is procedure to aid in improved wound healing. This negative pressure wound therapy can be used in cases of both acute and chronic wounds. Objectives: To find out pattern of wound healing while using vacuum assisted closure for healing chronic non healing ulcers. Materials and methods: It was a prospective study conducted among patients admitted to the Department of General Surgery. Participant included had chronic non healing ulcer due to various etiologies. The study period was from October 2021 to December 2021. 50 participants were enrolled into the study. The data was compiled and analyzed using SPSS version 26. Results: The wound healing was better after day 3. There was significant positive change in wound healing with P value of less than 0.05 over the follow up period. No other factor was found to influence wound healing. Conclusion: Vacuum assisted closure would enhance wound healing among those suffering from chronic non-healing ulcer.

Role of topical use of natural honey in chronic non healing ulcer: a prospective non randomized comparative trial on 150 patients

Background: Natural honey procured from any source on topical application on chronic non-healing ulcer has unique property to reduce pain, inflammation, oedema, deodorization, rapid disinfection, stimulate desloughing, promote neo vascularization, granulation, collagen synthesis, epithelialization and thus boost the process of ulcer healing.Methods: In this study a prospective, non-randomized trial was done on 150 patients divided in two groups of 75 each (group-A with honey dressing and group-B without honey dressing), of different age and sex having chronic non healing ulcers situated on various parts of the body. Natural honey available from various sources was used.Results: Most of the patients fall in their most productive and active 3rd and 4th decade of life. Pain and fever were the main reason of restricted mobility and absence from work reflecting productivity. Bacterial contamination, presence of necrotic tissue, bed ridden condition, old age, debility, DM, ulcer present in the vicinity of joint were found major cause of delay in the process of healing. The cost effectiveness, easy availability, ease of application makes natural honey a better alternative in the management of chronic non healing ulcer.Conclusions: Cost effectiveness, easy availability, ease of application, increasing healing process makes natural honey a better alternative in the management of chronic non healing ulcer and safe to use in diabetic patients as well.

Retained iatrogenic foreign body causing persistent non-healing wound: a case report

An 88-year-old female presented with non-healing wound of left hip, found to have iatrogenic foreign body. The patient presented at the age of 88 with complaints of a persistent wound of left hip. She had a previous incision and drainage of an abscess on her left hip and subsequently received negative pressure therapy. She underwent a wound exploration and found to have multiple foreign bodies in the wound. While uncommon, iatrogenic foreign body should be considered as a possible differential diagnosis in patient with non-healing wounds. The literature on iatrogenic foreign body is reviewed. Iatrogenic foreign body is an uncommon pathology but should be included in the differential diagnosis in patients presenting with a non-healing wound.

A comparative study between platelet rich plasma and conventional dressing in chronic non healing leg ulcers

Background: Chronic non-healing leg ulcers are a major health problem worldwide and have great impact on personal, professional and social levels, with high cost in terms of human and material resources. The present study was conducted with an aim to demonstrate the efficacy of autologous platelet rich plasma (PRP) in chronic non-healing leg ulcers in comparison to conventional dressings.Methods: A total of 50 patients with leg ulcers were randomized into two groups (A and B) with each group comprising of 25 patients each. Group A were treated with autologous platelet rich plasma (PRP) dressings and group B were treated with conventional dressings using normal saline. Ulcer measurements were taken on day 1, day 7, days 15 and after 30 days. The end point of study was complete wound epithelialization or appearance of granulation tissue, which ultimately lead to spilt skin grafting or secondary healing; whichever is earlier.Results: There was statistically significant difference in the average time taken for complete healing of ulcer in PRP dressings, 3.68 weeks against 6.2 weeks in conventional dressing group (p value <0.0001). PRP dressing group showed a 43.96% reduction in ulcer size as compared to 13.81% in conventional dressing group (p <0.0001). It was observed that PRP dressing group has faster wound healing and contraction of wound.Conclusions: PRP dressing of leg ulcers was better than conventional normal saline dressing as it leads to early reduction of ulcer size and enhances rate of wound healing.

Histopathological spectrum of chronic skin ulcers in a tertiary care hospital

Background:The skin is the largest organ of the body, comprising of epidermis, dermis and hypodermis. Thus, a wide range of diseases can develop from the skin ranging from infectious diseases to malignancy, some of which may present as non-healing ulcers. Skin biopsy forms the fundamental basis for differentiation of similar looking lesions, thus helping the pathologists to make a definitive diagnosis and more so to the clinician for better management of patients. The objective was to study the histopathological spectrum of chronic non healing ulcers of skin for proper management and treatment.Methods:This was a hospital-based study which was conducted in SKIMS,Soura, a tertiary care hospital of Kashmir valley for a period of 1year extending from January 2018 to December 2018. All the patients who presented with the complaint of non-healing ulcer for more than 4 to 6 weeks were subjected to skin biopsy and histopathological examination.Results:A total of 260 biopsies were examined. Out of 260 patients 146 were males and 114 were females. Ninety out of 260cases (34.61%) and 170 (65.39%) were diagnosed as malignant and benign ulcers respectively.Diabetic ulcer was the second most common cause ofnon-healing ulcers followed by bacterial infections and tuberculosis. Squamous cell carcinoma was the most common neoplastic pathology. Conclusions: It was concluded from the study that non-healing skin ulcers can be encountered at any age in daily medical practice

Subcutaneous mycosis presenting as a non- healing left calf ulcer in an immunocompromised patient

This is a case report of subcutaneous mycosis presenting as a non-healing left calf ulcer in an immunocompromised patient. Traumatic inoculation of the causative agent is the most likely route of infection. The diagnosis requires a detailed history and high clinical suspicion, confirmed by histopathological examination. The management requires a multidisciplinary team approach involving surgeon, pathologist, physician sub-specialised in infectious disease, wound care nursing team as well as social support services. The literature review recommended that the treatment of choice for such infection is surgical debridement in addition to optimal antifungal therapy.

The molecular biology in wound healing & non-healing wound / 中华创伤杂志(英文版)

The development of molecular biology and other new biotechnologies helps us to recognize the wound healing and non-healing wound of skin in the past 30 years. This review mainly focuses on the molecular biology of many cytokines (including growth factors) and other molecular factors such as extracellular matrix (ECM) on wound healing. The molecular biology in cell movement such as epidermal cells in wound healing was also discussed. Moreover many common chronic wounds such as pressure ulcers, leg ulcers, diabetic foot wounds, venous stasis ulcers, etc. usually deteriorate into non-healing wounds. Therefore the molecular biology such as advanced glycation end products (AGEs) and other molecular factors in diabetes non-healing wounds were also reviewed.

Difference of morphology and proliferation ability between diabetes mellitus-derived ADSCs and normal ADSCs / 中华医学美学美容杂志

Objective To investigate the morphological characteristics and proliferation ability of diabetes mellitus-derived adipose-derived stem cells (ADSCs) by comparing with normal-derived ADSCs.Methods The ADSCs could be achieved from diabetes mellitus' adipose tissue by the similar method of normal ADSCs isolation and culture,and then the differnce was compared between the two groups about their morphologies under microscope,and the proliferation ability of two groups was determined by CCK-8.Results ADSCs in patients with diabetes were obvious hypertrophy and irregular in morphology.A values of ADSCs in diabetes and non-diabetes were 0.210+0.002 and 0.390+0.006 in 1st day;0.250+0.015 and 0.443+0.023 in 2nd day;0.368+0.014 and 0.726+0.033 in 3rd day;0.368+0.014 and 0.726+0.033 in 4th day;1.767+0.072 and 3.153+0.067 in 5th day and 1.810+0.072and 3.170+0.021 in 6th day,respectively.The difference was statstically significant at the beginning from 4th day (P＜0.05).Conclusions There is obvious difference of the microscopic morphology between the diabetes mellitus-derived ADSCs and normal-derived ADSCs.The proliferation ability of the diabetes mellitus-derived ADSCs is lower than normal-derived ADSCs.These difference could be closely related to ulcerous non-healing wounds in patients with diabetes mellitus.

Infectious keratitis – a review.

Infectious keratitis is an important problem in the Indian context, and epidemiological studies suggest a higher prevalence of disease as compared to the developed world. Various aspects of the problem, including the host defence, ocular and systemic risk factors and microbial mechanisms that enhance pathogenesis have been discussed. The clinical and microbiological approach to the infected eye and patient and the relevant tests have been outlined. The major classes of medications that are used the methods of delivery are specified. Finally, the approach to patients with non-responsive keratitis that requires surgical manoeuvres is also highlighted. Clinical experience is important in distinguishing an infective from an inflammatory corneal pathology. The role of an experienced microbiologist is inevitable, for good clinical outcome. Therapeutic keratoplasty has to be done at the right time for better clinical outcomes.

Role of Autologous Platelet Derived Growth Factor and Fibrin Rich Plasma in Management of Chronic Non-healing Ulcer–A Pilot Study.

Background and Objectives: Chronic non-healing ulcer (CNHU) develops due to infections, trauma or underlying any medical and surgical conditions. Ulcer that have failed to response all available mode of treatment for long duration are more likely to develop gangrene and infection prone to limb amputation. This is a major public health problem. None of the conventional treatments are anticipated to stimulate active wound healing. The objectives of this study is to test the efficacy of topically applied autologous platelet derived growth factors and fibrin rich plasma in active repair of chronic non healing ulcer. Methods: Patients having one or more ulcers who have been receiving conventional treatment for their at least for more than 6 months duration but showed no evidence of healing till date were included in this study. Total of 30 skin ulcers were registered, of which 15 patients did not return for follow up. Rest 15 patients were included as the study group. All ulcers were treated with autologous platelet derived growth factors and fibrin rich plasma enriched antibiotic ointment. We observed that 73.33% ulcers were complete healed & rest ulcers had signs of improvement. Results: The study group showed complete healing in 73.33% ulcers and average 80% improvement observed in each ulcer, after applying autologous platelet derived growth factors and fibrin rich plasma. Significant ulcer healing was observed in patients who were less than 40 years of age, had no history of addiction for any toxic substance, and had ulcer size less than 30 sq cm. Ulcer healing rate was also found to be higher in cases whose duration of ulcer was within one year and those who did not have any history of systemic diseases. Conclusion: This study clearly shows the efficacy of topically applied autologous platelet derived growth factors and fibrin rich plasma in management of chronic non-healing ulcer.

Approach to Complex Wound Management and Adjunct Therapy

The ageing of our population and rise in chronic diseases has resulted in the complex profile of the patients in the community. Complex wounds such as diabetic foot ulcers, infected pressure ulcers and other complications of non-healing wounds are common encounters in the primary health settings. The challenges of these complex wounds lie in its multi-factorial nature of the person, the wound and the environment. This requires a team approach to care within the limited resources boundary. As part of the care continuum, it is essential for primary care physicians to be familiarized with the approach to care of complex wounds and the adjunct therapy. This article seeks to provide a broad framework using the systematic assessment framework via T.I.M.E (Tissue, Inflammation/Infection, Moisture imbalance, Epithelial edge of wound) for wound bed preparation to guide primary care physicians/clinicians in their approach to complex wounds. It also highlighted the complexities of chronic wound management pertaining to the person, the wound and the environment as well as the recent advances adjunct therapy in chronic wound care. In addition, it seeks to enable primary care physician and wound clinicians to translate wound-healing principles into effective management strategies to provide better clinical care to our patients.

A case of a 39-year-old immunocompromised Filipino male with non-healing wound of the right lower leg

This a case of a 39-year-old Filipino male with systemic lupus erythematosus (SLE) diagnosed in 2006, presenting with a 3-month history of non-healing wound on his right lower leg. This paper will discuss the etiologies of a non-healing wound and present an algorithm to guide the approach to diagnosis and management.

Port Site Infection in Laparoscopic Surgeries.

Background/Aims: As the surgeries undertaken by laparoscope are increasing, complications are also increasing. In light of the explosive increase in laparoscopic surgery, there is concern about the effectiveness of sterilizing reusable laparoscopic instruments which might be a potential source of infection if not properly sterilized. Our study explains port site infection, its diagnosis and management with review of literature. Setting and Design: This study was carried out in a tertiary care setting and was an outcome study. Material and Methods: All five patients in the study were operated (April 2008-2010) elsewhere and came to us for management of non healing sinuses. Result: Amongst operated cases of laparoscopic cholecystectomy one healed by irrigation with superoxide, two cases healed with sinus exploration and wound debridement while one case required extensive wound debridement requiring temporary mesh repair of the abdominal wall with removal of the mesh (due to persistence of sinus) six months later following complete healing, no residual hernia. One operated case of laparoscopic incisional hernia repair with laparoscopic Cholecystectomy healed after removal of mesh with sinus exploration. Conclusion: The present study is an attempt to make surgeons aware about the complications which occur due to improper sterilisation of laparoscopic instruments ending into increased morbidity of patients.

Treatment of Non-healing, Post-traumatic Wound with High Frequency Ultrasound of 10 MHz: A Case Report.

We present a case of a non-healing, post-traumatic wound, which as an alternative to reconstructive surgical intervention, was successfully treated with a non-invasive, highfrequency ultrasound of 10 MHz.