Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives

BACKGROUND Stem cell therapy has shown great potential for treating diabetic foot(DF).AIM To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades,with the aim of depicting the current global research landscape,identifying the most influential research hotspots,and providing insights for future research directions.METHODS We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF.Bibliometric analysis was carried out using CiteSpace,VOSviewer,and R(4.3.1)to identify the most notable studies.RESULTS A search was conducted to identify publications related to the use of stem cells for DF treatment.A total of 542 articles published from 2000 to 2023 were identified.The United States had published the most papers on this subject.In this field,Iran’s Shahid Beheshti University Medical Sciences demonstrated the highest productivity.Furthermore,Dr.Bayat from the same university has been an outstanding researcher in this field.Stem Cell Research&Therapy is the journal with the highest number of publications in this field.The main keywords were“diabetic foot ulcers,”“wound healing,”and“angiogenesis.”CONCLUSION This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years.Current research findings suggested that the hotspots in this field include stem cell dressings,exosomes,wound healing,and adipose-derived stem cells.Future research should also focus on the clinical translation of stem cell therapies for DF.

Surgical management of the diabetic foot:The current evidence

The prevalence of diabetes mellitus and its associated complications,particularly diabetic foot pathologies,poses significant healthcare challenges and economic burdens globally.This review synthesises current evidence on the surgical management of the diabetic foot,focusing on the interplay between neuropathy,ischemia,and infection that commonly culminates in ulcers,infections,and,in severe cases,amputations.The escalating incidence of diabetes mellitus underscores the urgency for effective management strategies,as diabetic foot complications are a leading cause of hospital admissions among diabetic patients,significantly impacting morbidity and mortality rates.This review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers,infections,and skeletal pathologies such as Charcot arthropathy,emphasising the critical role of early diagnosis,comprehensive management strategies,and interdisciplinary care in mitigating adverse outcomes.In addressing surgical interventions,this review evaluates conservative surgeries,amputations,and reconstructive procedures,highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot pathologies.The integration of advanced diagnostic tools,novel surgical techniques,and postoperative care,including offloading and infection control,are discussed in the context of optimising healing and preserving limb function.

Prognostic Factors for Diabetic Foot at CNHU-HKM

Introduction: Predictions on the prevalence of diabetes mellitus, according to the International Diabetes Federation, indicated 9.3% in 2019 and nearly 10.9% of the general population in 2045. In Benin, the increase in this prevalence, according to the World Health Organization (WHO), is constantly increasing. Diabetic foot is one of its most common complications. The aim of this work was to study the prognostic factors of diabetic foot in the Department of Endocrinology, Metabolism and Nutrition of the CNHU-HKM of Cotonou. Patients and method: This is a descriptive and analytical retrospective study of the prognostic factors of diabetic foot over a period of 3 years from January 2019 to December 2021 in patients who have been hospitalized or followed on an outpatient basis for diabetic foot in the Endocrinology, Metabolism and Nutrition Department of the CNHU-HKM of Cotonou. Results: A total of 112 patients were included in this study. The average age of the patients was 59.70 ± 2.10 years. A male predominance was noted with a sex ratio (M/F) of 1.7. Mixed gangrene and phlegmons were the most common lesions. According to the classification of diabetic feet according to the University of Texas, 59.1% of patients had a 100% risk of amputation. Ten patients died from sepsis (8.9%). The average blood glucose on admission was 2.74 ± 0.23 g/l, reflecting the glycemic imbalance in these patients. There is a statistically significant association between the duration of progression of diabetes, the type of lesion and amputation. Patients whose diabetes has lasted more than 30 years and patients who are not monitored have a greater risk of death. Conclusion: Diabetic patients most often consulted at a late stage, compromising conservative treatment. The duration of diabetes and the type of lesion on admission were the main factors leading to amputation, thus compromising the functional prognosis. As for death, it was mainly linked to irregular monitoring of diabetes and the duration of diabetes. Effective prevention and management of diabetic feet requires patient education about the diabetic foot and systematic screening of at-risk feet in consultation.

Portraying Diabetic Foot Ulcers: Comparative Evaluation of Diabetic Foot Infections versus Diabetic Foot Ulcers

Background: Confusion often arises in caring for diabetic foot infections and ulcers, especially with antimicrobials;we aim to shed light on this entity and alert healthcare workers to its stewardship. Methods: Records were reviewed between February 2016 and September 2023. Data for patients diagnosed with diabetes and foot ulcers, infected or not, were examined following ICD 9 search terms. Records for patients were included if they were prediabetic/diabetic adults with foot ulcers, more than 18 years old, and on antidiabetic treatment. Patients were excluded if they insulin resistant, with normal HgbA1c levels, wheel-chair dependent, bed-bound, non-diabetic patients, diabetic patients who had vascular lower limb surgery earlier to ulcers, diabetic patients who had aortocoronary bypass, deep venous thrombosis within six months, malignancy, and severe clinical depression. A modified IWGDF/IDSA guidelines definitions for DFI and DFU was considered. Statistical analysis was done using R programming. Statistical methods were employed as appropriate, and a significant P-value was considered for P Results: Most characteristics were well balanced between DFI and DFU, on imaging osteomyelitis and tissue swelling were significantly more in DFI. Endovascular radiological procedures showed angiograms to be considerably more in DFI, while angioplasty was more in DFU, in addition to smoking. Bacteremia was uncommon, and swab cultures were mostly polymicrobial in both ulcers;no clear association with blood bacteria was detected with the polymicrobial growth, though few were concordant. Antimicrobials prescribed for both ulcers were not statistically different except for carbapenems, which were more in DFI (P Conclusion: Attention should be paid to best practices while caring for diabetic ulcers. These include swab culture interpretations, the use of antimicrobials, and plan management according to DFI or DFU to utilize either local care or combination with antimicrobials.

Impact of tibial transverse transport in tissue regeneration and wound healing with perspective on diabetic foot ulcers

In this editorial,we comment on an article by Liao et al published in the current issue of the World Journal of Diabetes.We focus on the clinical significance of tibial transverse transport(TTT)as an effective treatment for patients with diabetic foot ulcers(DFU).TTT has been associated with tissue regeneration,improved blood circulation,reduced amputation rates,and increased expression of early angiogenic factors.Mechanistically,TTT can influence macrophage polarization and growth factor upregulation.Despite this potential,the limitations and conflicting results of existing studies justify the need for further research into its optimal application and development.These clinical implications highlight the efficacy of TTT in recalcitrant DFU and provide lasting stimuli for tissue re-generation,and blood vessel and bone marrow improvement.Immunomodu-lation via systemic responses contributes to its therapeutic potential.Future studies should investigate the underlying molecular mechanisms to enhance our understanding and the efficacy of TTT.This manuscript emphasizes the potential of TTT in limb preservation and diabetic wound healing and suggests avenues for preventive measures against limb amputation in diabetes and peripheral artery disease.Here,we highlight the clinical significance of the TTT and its importance in healing DFU to promote the use of this technique in tissue regeneration.

Home-based Detection and Prediction of Diabetic Foot Ulcers at Early Stage Using Sensor Technology and Supervised Learning

For years,foot ulcers linked with diabetes mellitus and neuropathy have significantly impacted diabetic patients’ health-related quality of life(HRQoL). Diabetes foot ulcers impact15% of all diabetic patients at some point in their lives. The facilities and resources used for DFU detection and treatment are only available at hospitals and clinics,which results in the unavailability of feasible and timely detection at an early stage. This necessitates the development of an at-home DFU detection system that enables timely predictions and seamless communication with users,thereby preventing amputations due to neglect and severity. This paper proposes a feasible system consisting of three major modules:an IoT device that works to sense foot nodes to send vibrations onto a foot sole,a machine learning model based on supervised learning which predicts the level of severity of the DFU using four different classification techniques including XGBoost,K-SVM,Random Forest,and Decision tree,and a mobile application that acts as an interface between the sensors and the patient. Based on the severity levels,necessary steps for prevention,treatment,and medications are recommended via the application.

Prevalence and risk factors of wound complications after transtibial amputation in patients with diabetic foot

BACKGROUND Diabetic foot(DMF)complications are common and are increasing in incidence.Risk factors related to wound complications are yet to be established after transtibial amputation under the diagnosis of DMF infection.AIM To analyze the prognosis and risk factors related to wound complications after transtibial amputation in patients with diabetes.METHODS This retrospective cohort study included seventy-two patients with DMF complications who underwent transtibial amputation between April 2014 and March 2023.The groups were categorized based on the occurrence of wound complications,and we compared demographic data between the complication group and the non-complication group to analyze risk factors.Moreover,a multivariate logistic regression analysis was performed to identify risk factors.RESULTS The average follow-up period was 36.2 months.Among the 72 cases,31(43.1%)had wound complications.Of these,12 cases(16.7%)received further treatment,such as debridement,soft tissue stump revision,and re-amputation at the proximal level.In a group that required further management due to wound complications after transtibial amputation,the hemoglobin A1c(HbA1c)level was 9.32,while the other group that did not require any treatment had a 7.54 HbA1c level.The prevalence of a history of kidney transplantation with wound complications after transtibial amputation surgery in DMF patients was significantly greater than in cases without wound complications(P=0.02).Other factors did not show significant differences.CONCLUSION Approximately 43.1%of the patients with transtibial amputation surgery experienced wound complications,and 16.7%required additional surgical treatment.High HbA1c levels and kidney transplant history are risk factors for postoperative wound complications.

Therapeutic Effectiveness of Leukocyte-and Platelet-rich Fibrin for Diabetic Foot Ulcers:A Retrospective Study

Objective Diabetic foot ulcer(DFU)is one of the most serious complications of diabetes.Leukocyte-and platelet-rich fibrin(L-PRF)is a second-generation autologous platelet-rich plasma.This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice.Methods Patients with DFU who received L-PRF treatment and standard of care(SOC)from 2018 to 2019 in Tongji Hospital were enrolled.The clinical information including patient characteristics,wound evaluation(area,severity,infection,blood supply),SOC of DFU,and images of ulcers was retrospectively extracted and analyzed.L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction(PVR)greater than 80%.Therapeutic effectiveness,including overall PVR and the overall and weekly healing rates,was evaluated.Results Totally,26 patients with DFU were enrolled,and they had an ulcer duration of 47.0(35.0,72.3)days.The severity and infection of ulcers varied,as indicated by the Site,Ischemia,Neuropathy,Bacterial Infection,and Depth(SINBAD)scores of 2–6,Wagner grades of 1–4,and the Perfusion,Extent,Depth,Infection and Sensation(PEDIS)scores of 2–4.The initial ulcer volume before L-PRF treatment was 4.94(1.50,13.83)cm3,and the final ulcer volume was 0.35(0.03,1.76)cm3.The median number of L-PRF doses was 3(2,5).A total of 11 patients achieved complete epithelialization after the fifth week of treatment,and 19 patients achieved at least an 80%volume reduction after the seventh week.The overall wound-healing rate was 1.47(0.63,3.29)cm3/week,and the healing rate was faster in the first 2 weeks than in the remaining weeks.Concurrent treatment did not change the percentage of complete epithelialization or healing rate.Conclusion Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index,SINBAD score,or Wagner grade,indicating that this method is appropriate for DFU treatment under different clinical conditions.

Adipose-derived stem cells in diabetic foot care:Bridging clinical trials and practical application

Diabetic foot ulcers(DFUs)pose a critical medical challenge,significantly impairing the quality of life of patients.Adipose-derived stem cells(ADSCs)have been identified as a promising therapeutic approach for improving wound healing in DFUs.Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU,its clinical applications remain elusive.In this review,we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs.The review begins with a discussion of the classification and clinical management of diabetic foot conditions.It then discusses the current landscape of clinical trials,focusing on their geographic distribution,reported efficacy,safety profiles,treatment timing,administration techniques,and dosing considerations.Finally,the review discusses the preclinical strategies to enhance ADSC efficacy.This review shows that many trials exhibit biases in study design,unclear inclusion criteria,and intervention protocols.In conclusion,this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches,with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers

BACKGROUND Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability,traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method.AIM To investigate whether Huangma Ding or autologous platelet-rich gel(APG)treatment would benefit diabetic lower extremity arterial disease(LEAD)patients with foot ulcers.METHODS A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups:Group A(62 patients;basal treatment),Group B(38 patients;basal treatment and APG),and Group C(55 patients;basal treatment and Huangma Ding).All patients underwent routine follow-up visits for six months.After follow-up,we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters.RESULTS The infection status of the three groups before treatment was the same.Procalcitonin(PCT)improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B.Logistic regression analysis revealed that PCT was positively correlated with total amputation,primary amputation,and minor amputation rates.The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A.The major amputation rate,minor amputation rate,and total amputation times in Groups B and C were lower than those in Group A.CONCLUSION Our research indicated that diabetic foot ulcers(DFUs)lead to major amputation,minor amputation,and total amputation through local infection and poor microcirculation and macrocirculation.Huangma Ding and APG were effective attreating DFUs.The clinical efficacy of Huangma Ding was better than that of autologous platelet gel,which may be related to the better control of local infection by Huangma Ding.This finding suggested that in patients with DFUs combined with coinfection,controlling infection is as important as improving circulation.

Clinical comprehensive treatment protocol for managing diabetic foot ulcers:A retrospective cohort study

BACKGROUND Diabetic foot ulcers(DFUs)are a common complication of diabetes,often leading to severe infections,amputations,and reduced quality of life.The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications.A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs.The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing,reduced amputation rates,and improved overall patient outcomes compared to standard treatment protocols.AIM To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol.METHODS This retrospective study included 62 patients with DFUs,enrolled between January 2022 and January 2024,randomly assigned to the experimental(n=32)or control(n=30)group.The experimental group received a comprehensive treatment comprising blood circulation improvement,debridement,vacuum sealing drainage,recombinant human epidermal growth factor and anti-inflammatory dressing,and skin grafting.The control group received standard treatment,which included wound cleaning and dressing,antibiotics administration,and surgical debridement or amputation,if necessary.Time taken to reduce the white blood cell count,number of dressing changes,wound healing rate and time,and amputation rate were assessed.RESULTS The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate,wound healing time,and amputation rate.Additionally,the comprehensive treatment protocol was safe and well tolerated by the patients.CONCLUSION Comprehensive treatment for DFUs is more effective than standard treatment,promoting granulation tissue growth,shortening hospitalization time,reducing pain and amputation rate,improving wound healing,and enhancing quality of life.

Use of Topical Complementary and Alternative Medicines (CAM) in Diabetic Septic Foot Disease in Makkah Region, Western of Saudi Arabia, an Exploratory Study

Diabetes is a chronic condition that is significantly impacted daily by environment. At least one in five Saudis, suffer from diabetes. “Diabetes is a pandemic of unprecedented magnitude spiraling out of control” (Boulton). Saudi Arabia ranks the second highest in the Middle East, and is the seventh in the world for the prevalence of diabetes (WHO). Diabetes mellitus (DM) has been found to be related to high mortality, morbidity accompanied by poor general health and lower quality of life. Current Saudi diabetes patients’ behaviors, practices, and beliefs regarding foot health problems such as ulcers, are not well investigated. Diabetic patients frequently utilize natural remedies and Herbs for self-medication as a part of complementary and alternative Medicine. Aim of study: To explore the widespread use of the alternative remedies in the local communities of the Western Saudi Arabia, the drives behind using and to focus on the potential adverse effects following their usage. Method: A descriptive, cross-sectional study of 386 diabetic patients with feet problems in Makkah Region, West of Saudi Arabia during the period April - June 2023. Results: Out of the 531 participants, only 386 participants reported diabetic foot disorder (DFD). Most of the participant were above 65 years of age group (24.61 %). Male (52.08%) more than female (47.92%) in the research group. All of the participants had diabetic foot disorders at least once. The prevalence of complementary and alternative medicines (CAM) use among them was 67.88%, as solitary or in combination with hospital medicines. Honey headed the list followed by myrrh and black seeds. Acquaintances advice (59.54%) was the most reason for using the alternative medicine. 60.30% of Diabetic foot patient complained of adverse effects during CAM remedies use. Conclusion: Consumption of CAM remedies among diabetic patients for Diabetic Foot Disorder (DFD) is common. Honey headed the list followed by myrrh and black seeds. Additional wide-scale research is required to establish their actual efficacy, safety and potential adverse out-comes and to generalize the outcomes.

The Effect of Transverse Tibial Bone Transfer in the Treatment of Diabetic Foot

To analyse the effectiveness of performing a transverse tibial bone graft in the treatment of patients with diabetic foot. We retrospectively analysed the clinical details of 51 diabetic foot patients in our hospital from February 2023 to February 2024 and divided them into two groups according to the different treatment modalities, in which the control group received open debridement and the treatment group received transverse tibial bone transfer and compared the differences between the two groups. There were large differences in VAS score, Toronto Clinical Symptom Score, quality of life score, internal lumen diameter, blood flow velocity in the affected limb, perfusion volume, vascular endothelial growth factor, epidermal growth factor and CRP between the two groups after surgery (P < 0.05). Patients with diabetic foot should be treated with transverse tibial bone grafting, which is safer and more effective and can have a significant impact on improving the status of the affected limb, the inflammation and the patient’s quality of life.

Effectiveness of topical oxygen therapy in wound healing for patients with diabetic foot ulcer

Objectives:Non-healing wounds have been one of the major challenges in health care because of increased morbidity,especially for those who have diabetes mellitus.Numerous regimens are being innovated to produce an evidence-based practice that would minimize complications and promote healing.Topical oxygen therapy is an innovation in wound care that has been considered influential in the wound healing process.This intervention aims to increase the oxygen concentration in the affected limb to promote wound healing.Methods:This research applied an experimental design that targeted a total of 60 adult patients aged 45–64 years with diabetic foot ulcers.A randomized systematic sampling technique was used to allow equal chances and prevent bias.In total,30 patients in the control group received usual care for diabetic foot ulcers,and the remaining 30 patients in the experimental group received topical oxygen therapy together with standard care for diabetic foot ulcers.Subjects were assessed using the Wagner-Meggitt Wound Classification System.Results:The result proved that there was a significant difference in the wound grade of patients in the experimental group after the application of the usual wound care plus the topical oxygen therapy using Friedman's test.The control and experimental groups were compared using Mann–Whitney statistical analyses,and the results showed that there was a significant difference between the control and experimental groups after the application of topical oxygen therapy.Conclusions:Topical oxygen therapy was demonstrated to be effective to aid in the wound healing process of patients with diabetic foot ulcers.Fur ther research was recommended to improve the application of topical oxygen therapy to patients with chronic wounds and promote the wound healing process.

A Case Report of Diabetic Foot Ulcer Treated by Herbal Food Homology Therapy

Diabetic foot ulcer (DFU) is a common and severe complication among patients with diabetes. There are hundreds of natural products derived from herbs that have been identified and proven to be effective for glucose-lowering and wound-healing effects, such as flavones. In this case study, we reported that a 76-year-old male patient with severe traumatic DFU was cured after drinking yellow tea (dehydrogenated Camellia sinensis) as a postprandial auxiliary treatment for six months. Previously, the patient was required to be hospitalized, but the wound deteriorated after five months. The patient drank yellow tea at approximately 12:30 pm (the active time of heart meridian) after lunch every day. Five grams of yellow tea were boiled in one liter of water and covered above 70°C for approximately 30 minutes. He experienced profuse sweating on his back after drinking yellow tea, with no other adverse effects. His lifestyle and healthcare remained constant except for replacing green tea with yellow tea. After six months, the ulcer had completely healed, and after one year of follow-up, no new abnormalities or side effects were found. This self-controlled case study indicates that flavone-enriched yellow tea or other herbs may be an auxiliary therapy for diabetes and its complications.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Current scenario of traditional medicines in management of diabetic foot ulcers:A review

Diabetic foot infections and diabetic foot ulcers(DFU)cause significant suffering and are often recurring.DFU have three important pathogenic factors,namely,microangiopathy causing local tissue anoxia,neuropathy making the foot prone to injuries from trivial trauma,and local tissue hyperglycaemia favouring infection and delaying the wound healing.DFU have been the leading cause for non-traumatic amputations of part or whole of the limb.Western medicines focus mainly on euglycaemia,antimicrobials,debridement and wound cover with grafts,and off-loading techniques.Advances in euglycaemic control,foot care and footwear,systemic antimicrobial therapy,and overall health care access and delivery,have resulted in an overall decrease in amputations.However,the process of wound care after adequate debridement remains a major cost burden globally,especially in developing nations.This process revolves around two basic concerns regarding control/eradication of local infection and promotion of faster healing in a chronic DFU without recurrence.Wound modulation with various dressings and techniques are often a costly affair.Some aspects of the topical therapy with modern/Western medicines are frequently not addressed.Cost of and compliance to these therapies are important as both the wounds and their treatment are“chronic.”Naturally occurring agents/medications from traditional medicine systems have been used frequently in different cultures and nations,though without adequate clinical base/relevance.Traditional Chinese medicine involves restoring yin-yang balance,regulating the‘chi’,and promoting local blood circulation.Traditional medicines from India have been emphasizing on‘naturally’available products to control wound infection and promote all the aspects of wound healing.There is one more group of chemicals which are not pharmaceutical agents but can create acidic milieu in the wound to satisfy the above-mentioned basic concerns.Various natural and plant derived products(e.g.,honey,aloe vera,oils,and calendula)and maggots are also used for wound healing purposes.We believe that patients with a chronic wound are so tired physically,emotionally,and financially that they usually accept native traditional medicine which has the same cultural base,belief,and faith.Many of these products have never been tested in accordance to“evidence-based medicine.”There are usually case reports and experience-based reports about these products.Recently,there have been some trials(in vitro and in vivo)to verify the claims of usage of traditional medicines in management of DFU.Such studies show that these natural products enhance the healing process by controlling infection,stimulating granulation tissue,antimicrobial action,promoting fibroblastic activity and collagen deposition,etc.In this review,we attempt to study and analyse the available literature on results of topical traditional medicines,which are usually advocated in the management of DFU.An integrated and‘holistic’approach of both modern and traditional medicine may be more acceptable to the patient,cost effective,and easy to administer and monitor.This may also nevertheless lead to further improvement in quality of life and decrease in the rates of amputations for DFU.

Inflammation in diabetic retinopathy: possible roles in pathogenesis and potential implications for therapy

Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine

Diabetic peripheral neuropathy(DPN)is one of the strongest risk factors for diabetic foot ulcers(neuropathic ulcerations)and the existing ulcers may further deteriorate due to the damage to sensory neurons.Moreover,the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time.DPN is associated with gut microbiota dysbiosis.Traditional Chinese medicine(TCM)compounds such as Shenqi Dihuang Decoction,Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota.The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut microbiota.

Diabetic foot ulcer:A comprehensive review of pathophysiology and management modalities

Diabetic foot ulcer (DFU) is a debilitating and severe manifestation ofuncontrolled and prolonged diabetes that presents as ulceration, usually locatedon the plantar aspect of the foot. Approximately 15% of individuals with diabeteswill eventually develop DFU, and 14%-24% of them will require amputation ofthe ulcerated foot due to bone infection or other ulcer-related complications. Thepathologic mechanisms underlying DFU are comprise a triad: Neuropathy,vascular insufficiency, and secondary infection due to trauma of the foot.Standard local and invasive care along with novel approaches like stem celltherapy pave the way to reduce morbidity, decrease amputations, and preventmortality from DFU. In this manuscript, we review the current literature withfocus on the pathophysiology, preventive options, and definitive management ofDFU.