OBJECTIVETo study the mechanism of treating diabetic foot by clearing heat, detoxification, activating blood, and dredging collaterals method.

METHODSSixty diabetic foot patients were randomly assigned to the treatment group and the control group, 30 cases in each group. On the basis of the same routine treatment, patients in the treatment group were treated by Qingjie Tongluo Recipe (QTR) plus external washing of Chinese herbs plus external dressing by herbs with removing necrosis and promoting granulation actions, while those in the control group were treated with routine aseptic external dressing. Three months was taken as one therapeutic course. The wound area and basic fibroblast growth factor (bFGF) were detected before and after treatment. The content of vascular endothelial growth factor (VEGF), the peripheral vascular and nerve functions were also measured. The therapeutic effects were also observed.

RESULTSAfter treatment, in the treatment group,15 patients were cured, 12 markedly effective, 2 effective, 1 ineffective, the cure rate was 50.0% and the total effective rate was 96.7%, while in the control group, 9 cases were cured, 6 markedly effective, 8 effective, 7 ineffective, the cure rate was 30.0% and the total effective rate was 76.7%. The total effective rate was better in the treatment group than in the control group (P <0. 01). The contents of bFGF and VEGF were significantly higher in the two groups after treatment (P <0.01). Besides, better results were obtained in the treatment group (P < 0.01). The blood flow speed of the dorsalis pedis artery, the inner diameter of the dorsalis pedis artery, and the common peroneal nerve conduction velocity were somewhat improved (P <0.05, P <0.01). Besides, better results were obtained in the treatment group (P <0.01).

CONCLUSIONSQTR combined external washing plus external dressing by herbs with removing necrosis and promoting granulation actions could promote the healing of diabetic foot induced ulcers, improve the vascular and nerve functions. Its efficacy was superior to that of the control group.

Aged ; Diabetic Foot ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy

Chronic wounds such as diabetic foot ulcers are epidemic, which bring huge burdens to both the patients and the society. However, with current treatment methods, diabetic foot ulcers often heal poorly and recur frequently, so it is urgent and important to find new and advanced therapies. Stem cell therapy has been proved by a large number of pre-clinical and clinical studies as a potential treatment for chronic wounds. However, the acquisition of stem cells often depends on invasive techniques, and immunogenicity and limited cell survival in vivo also limit the large-scale application and promotion of stem cell therapy. In the recent years, with the development and advance of induced pluripotent stem cell (iPSC) technology, it has shown a strong translational potential in the treatment of chronic wounds such as diabetic foot ulcers. This article reviews the applications and prospect of iPSCs in animal wound healing models including diabetic ulcers and limb ischemia, the limitations of their clinical application, and the methods to improve their safety.
Animals ; Diabetes Mellitus ; Diabetic Foot/drug therapy* ; Induced Pluripotent Stem Cells ; Wound Healing

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.
Humans ; Ulcer/therapy* ; Medicine, Chinese Traditional ; Beclin-1 ; Quality of Life ; Wound Healing ; Diabetes Complications ; Autophagy ; Diabetic Foot/drug therapy* ; Diabetes Mellitus/genetics*

OBJECTIVETo assess the efficacy and safety of Tangzu Yuyang Ointment (TYO) for treatment of chronic diabetic foot ulcers.

METHODSFifty-seven patients with chronic diabetic foot ulcers of Wagner's ulcer grade 1 to 3 were randomly assigned to the control group (29 cases) and the treatment group (28 cases). Patients in the control group received the standard wound therapy (SWT), while those in the treatment group received SWT plus TYO. The ulcer healing rate, the ulcer improvement rate and the incidence of adverse events were compared between the two groups. Totally 48 patients finished the final follow-ups and entered the data analysis.

RESULTSThe ulcer improvement rate was 79.2% in the TYO group and 41.7% in the SWT group (P=0.017) at the 12th week, and 91.7% vs. 62.5% (P=0.036) at the 24th week. There was no statistical difference in the ulcer healing rate and the incidence of adverse events between the two groups at week 4, 12, and 24, respectively. The ulcer healing time was 96 +/- 56 days in the TYO group and 75 +/- 53 days in the SWT group, showing insignificant difference (P=0.271).

CONCLUSIONTYO plus SWT was more safe and effective than SWT alone in the treatment of chronic diabetic foot ulcers.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Diabetic Foot ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Ointments ; Phytotherapy ; Treatment Outcome ; Wound Healing ; Young Adult

OBJECTIVETo investigate the effects of local injection of insulin on the level of systemic blood glucose and granulation tissue formation of wound in patients with diabetic foot ulcer.

METHODSThirty-two patients with diabetic foot ulcer hospitalized in our wards from June 2009 to June 2010 were divided into insulin (I, n = 16) and control (C, n = 16) groups according to the random number table. For patients in I group, after debridement, one half of calculated dose of insulin diluted with equal amount of normal saline was injected diffusely into the base of the ulcer, and another half dose of insulin was subcutaneously injected into abdominal wall for 7 days, two times a day. For patients in C group, after debridement, primary insulin was subcutaneously injected into abdominal wall, 1 mL saline was subcutaneously injected into basal layer of ulcer for 7 days, two times a day. Before injection and 0.5, 1.0, 2.0, and 4.0 hours after injection (PIH), level of fasting blood glucose was determined. Before injection and on post injection day (PID) 3, 5, and 7, the growth of granulation tissue was assessed, and wound specimens were harvested for observation of CD34 expression and calculation of microvessel density (MVD). Data were processed with t test.

RESULTSThe levels of fasting blood glucose in both groups during observational time points ranged from 6.6 mmol/L to 12.8 mmol/L with a mean of (10.0 ± 2.2) mmol/L, and there was no statistical difference (with t values from 0.000 to 2.209, P values all above 0.05). Growth of granulation tissue in I group was more exuberant from PID 5, especially on PID 7 [(59.06 ± 1.58)%], which was significantly richer than that in C group [(23.61 ± 1.57)%, t = 17.420, P = 0.000]. New vessels were observed in I group from PID 3 as indicated by CD34 expression. There was no obvious difference in the number of MVD between I group and C group on PID 3 (t = 0.247, P > 0.05). The number of MVD per 200 times visual field in I group was respectively 8.34 ± 0.48, 11.22 ± 0.97 on PID 5 and 7, which was respectively higher than that in C group (4.42 ± 0.14, 5.44 ± 1.13, with t value respectively 16.568, 27.664, P values all below 0.01).

CONCLUSIONSLocal injection of insulin has a significant effect on systemic blood glucose in patients with diabetic foot ulcer, and it can promote the growth of granulation tissue and wound healing.

Adult ; Aged ; Aged, 80 and over ; Blood Glucose ; metabolism ; Diabetic Foot ; drug therapy ; metabolism ; Female ; Humans ; Injections ; Insulin ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Wound Healing

To analyze the outcome indicators from the randomized controlled trials(RCTs) on traditional Chinese medicine(TCM) treatment for diabetic foot, and to lay a foundation for the establishment of the core index set of the clinical trials on TCM treatment of diabetic foot. Computer retrieval of RCTs on TCM treatment of diabetic foot was performed in CNKI, Wanfang, SinoMed, PubMed, Cochrane Library, EMbase and Web of Science databases. Literature screening and data extraction were conducted independently by two researchers in strict accordance with inclusion and exclusion criteria. Any difference was resolved through discussion. A total of 72 RCTs involving 5 791 patients were included and 204 indicators were used. The number of indicators used in a single study was 2-22, with an average of 3 indicators used for each RCT. The indicators with top 16 frequency were clinical total effective rate, ankle brachial index(ABI), ulcer area, TCM syndrome integral, fibrinogen(FIB), fasting blood glucose(FBG), plasma viscosity(PV), c-reactive protein(CRP), saccharification blood of eggs(HbAlc), 2 h postprandial blood glucose(2 hPG), wound healing time, triglyce-rides(TC), TCM efficacy for syndromes, total cholesterol(TG), percutaneous oxygen partial pressure(TCPO2) and TCM symptom scores. The difference in selection of RCT indicators was large among TCM treatment methods for diabetic foot, and the combination of outcome indicators was arbitrary. The description on indexes was not standardized. Some non-laboratory examination indicators, some indicators not recommended in guidelines or not recognized in clinical practice, and some self-made indicators were not explained in detail. There was a lack of standardized evaluation criteria for indicators. The indicators had large time-point difference in measurement, and the time points were not distinguished in the measurement for diabetic foot patients with different degrees of severity. In addition, the patients with long course of treatment weren't timely measured. The characteristics of TCM or significant endpoint indicators were insufficient. It was urgent to establish the core index set of TCM in treating diabetic foot.
Blood Glucose ; Diabetes Mellitus ; Diabetic Foot/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome

Chemical constituents of the Fufang Huangbai Ye( FFHB) were analyzed and identified by UPLC-ESI-LTQ-OrbitrapMS. The analysis was performed on an Waters HSS T3 reverse phase column( 2. 1 mm×100 mm,1. 8 μm). The mobile phase consisting of 0. 1% aqueous formic acid( A) and acetonitrile( B) was used with gradient elution,and the flow rate was 0. 3 mL·min~(-1).Based on the information of the accurate mass,the multistage fragment ions,the mass spectrometric data of the standard substance and the relative reference literature,the structure of the chemical constituents in FFHB were identified. Based on the identified compounds,network pharmacology study,including target prediction,functional enrichment,and molecular docking was applied to screen out the main active substances for treatment of diabetes foot and explore the potential mechanism. The results showed that a total of 138 compounds were identified,including 28 alkaloids,16 flavonoids,11 phenylethanoid glycosides,9 cycloolefins,11 cyclohexylethanol derivatives,28 phenolic acids and derivatives,3 lignans,4 terpenes,28 volatile oils and the others. Further,36 active substances for diabetes foot were screened out,and the functional enrichment showed the potential mechanism of FFHB were mainly seven functional items including inflammatory response,growth factor activity. This study combining the UPLC-LTQ-Orbitrap-MS technology and the network pharmacology provide a useful reference and basis for active compounds,quality control markers and the pharmacological mechanism of FFHB for diabetic foot treatment.
Chromatography, High Pressure Liquid ; Diabetic Foot ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Mass Spectrometry ; Molecular Docking Simulation ; Phytochemicals ; isolation & purification ; pharmacology

OBJECTIVE: To investigate the clinical effect of vancomycin bone cement in the treatment of diabetic foot ulcer (DFU) ruptured Wagner gradeⅡ-Ⅳ. METHODS: From March 2019 to April 2021, 32 patients with Wagner gradeⅡ-Ⅳ diabetic foot were divided into vacuum sealing drainage (VSD) group and bone cement group according to different treatment methods. There were 16 cases in VSD group, 8 males and 8 females;the age ranged from 66 to 81 (70.50±7.20) years, and the course of disease ranged from 8 to 40 (27.56±8.55) months;Wagner gradeⅡin 2 cases, grade Ⅲin 7 cases and grade Ⅳin 7 cases;debridement and VSD were used. There were 16 cases in the bone cement group, 9 males and 7 females;the age ranged from 63 to 79 (69.56±7.29) years, and the course of disease ranged from 11 to 39(22.75±11.43) months;Wagner gradeⅡ in 2 cases, grade Ⅲin 5 cases and grade Ⅳ in 9 cases;vancomycin loaded bone cement was used for treatment. The types of bacteria, negative time of bacterial culture, skin healing time, hospital stay, operation times and complications were observed and compared between two groups. RESULTS: All patients were followed up for 3 to 6 (4.00±1.07) months. The bacterial negative time, skin healing time and hospital stay in bone cement group were significantly lower than those in VSD group ( CONCLUSION Vancomycin loaded bone cement is effective in the treatment of Wagner grade Ⅱ-Ⅳ diabetic foot ulceration wounds. It can reduce the length of hospital stay, shorten the healing time of skin and kill pathogens as soon as possible. It is one of the effective methods to treat Wagner gradeⅡ-Ⅳdiabetic foot ulceration.
Bone Cements/therapeutic use* ; Child ; Child, Preschool ; Diabetes Mellitus ; Diabetic Foot/drug therapy* ; Female ; Humans ; Male ; Treatment Outcome ; Vancomycin ; Wound Healing

INTRODUCTIONThe prevalence of diabetes mellitus is high in Singapore. Infections of the lower limb are significant causes of morbidity in this population. Although the aerobic bacteriology of these infections is well-documented, there is less data available on the anaerobic pathogens involved. This study sets out to describe the anaerobic bacteria associated with diabetic foot infections, and evaluates the susceptibility to 3 antimicrobials with anaerobic activity.

MATERIALS AND METHODSAnaerobic culture was performed on operative samples taken from diabetic foot infections. Organisms were identified through standard microbiological methods and commercial identification kits. Antimicrobial susceptibility testing to clindamycin, metronidazole and imipenem was performed by agar dilution.

RESULTSOne hundred and two strains of strict anaerobic bacteria were isolated from 30 unique specimens. The predominant anaerobic isolates were Peptostreptococcus spp. (46%) and Bacteroides fragilis group (19%). Antibiotic resistance was detected for clindamycin (18%), metronidazole (1%) and imipenem (2%).

CONCLUSIONMultiple anaerobic species can be isolated from diabetic foot infections. A significant proportion of isolates are resistant to clindamycin, while resistance to imipenem and metronidazole remains low.

Anti-Bacterial Agents ; therapeutic use ; Bacteria, Aerobic ; drug effects ; genetics ; isolation & purification ; DNA, Bacterial ; analysis ; Diabetic Foot ; surgery ; Drug Resistance, Multiple, Bacterial ; Drug Therapy, Combination ; Humans ; Nucleic Acid Amplification Techniques ; Retrospective Studies ; Surgical Wound Infection ; drug therapy ; microbiology

OBJECTIVETo investigate the clinical effects of composite salvia injection (CSI) matched with western medicine (WM) in treating diabetic foot.

METHODSSeventy-two patients, whose diagnosis were confirmed to be diabetic foot, were randomly divided and equally distributed into the comprehensive CSI plus WM treated group and the WM control group, they were treated with the CSI and WM treatment and the conventional WM respectively. The therapeutic effect was evaluated in combining with data of electromyogram and hemorrheologic investigation.

RESULTSAll the indexes were improved to various extent after treatment in both groups, but there was more significant in the CSI group than in the WM group, shown as quickening of motor and sensory nerve conduction velocity of median nerve and lowering of blood viscosity, as compared with those before treatment, P < 0.01.

CONCLUSIONCSI matched with WM in treating diabetic foot is beneficial for resulting in better effect.

Aged ; Diabetes Mellitus, Type 2 ; drug therapy ; Diabetic Foot ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Infusions, Intravenous ; Insulin ; therapeutic use ; Male ; Middle Aged ; Phytotherapy ; Salvia miltiorrhiza