Qingre Baidu mixture-induced effect of AI-2 on Staphylococcus aureus and Pseudomonas aeruginosa biofilms in chronic and refractory wounds.

The present study aimed to investigate the effect of the traditional Chinese medicine Qingre Baidu mixture (QBM) on the regulation of various parameters, including the morphology of bacterial biofilms, the bacterial density sensing system, the self-induction of the molecule autoinducer (AI)-2 and the hypoxia-inducible factor (HIF)-vascular endothelial growth factor (VEGF) signaling pathway. For that purpose, Sprague Dawley rats were administered the QBM, the Wu Wei Xiao Du Wan drink (WXD) and cefoperazone (Cef) prior to drug isolation from serum. Vibrio harveyi BB170 was employed as a reporter strain to detect the AI-2 signaling pathway in Staphylococcus aureus and Pseudomonas aeruginosa. The expression of HIF-1α and VEGF expression was examined by immunohistochemistry. ELISAs were used to measure the expression of HIF-1α, HIF-2α, HIF-3α and VEGF. The level of inflammation was evaluated by hematoxylin and eosin staining. Biofilm formation and the number of macrophages were detected by immunofluorescence. The results revealed that the QBM could reduce the concentration of AI-2 derived from Staphylococcus aureus and Pseudomonas aeruginosa, and markedly increase the levels of HIF-1α, HIF-2α and VEGF in chronic and refractory wounds. The QBM strongly inhibited the formation of bacterial biofilms and the number of macrophages, therefore promoting wound healing. In conclusion, the QBM could inhibit the biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa through decreasing the levels of AI-2 while upregulating the expression of HIF-1α, HIF-2α and HIF-3α, which increased the levels of VEGF, thereby promoting angiogenesis and wound healing in chronic and refractory wounds.

Combined antegrade femoral artery and retrograde popliteal artery recanalization for chronic occlusions of the superficial femoral artery.

PURPOSE: To evaluate the efficacy and safety of a dual femoral-popliteal approach in the supine position after failed antegrade recanalization attempts in chronic total occlusion (CTO) of the superficial femoral artery (SFA). MATERIALS AND METHODS: From May 2011 to October 2012, 21 patients underwent dual femoral-popliteal recanalization for CTO of the SFA, with a mean lesion length of 87.4 mm ± 5.8. When contralateral antegrade recanalization of SFA occlusions via the common femoral artery could not be achieved, the occlusions were intrainterventionally accessed by retrograde approach via the popliteal artery, which was punctured anteriorly with gently flexed knee and crus extorsion. When the SFA had been recanalized, further angioplasty and stent placement procedures were completed via the femoral artery. RESULTS: A technical success rate of 100% (entailing puncture of the popliteal artery and SFA recanalization) was achieved, and no hemorrhage, hematoma, pseudoaneurysm, arteriovenous fistula, or other complications developed. During a mean follow-up of 9.8 months ± 1.5, claudication severity, rest pain, and toe ulcers improved significantly. The pulse of the distal arteries, as well as the filling of the veins, could be distinctly felt. Ankle-brachial index changed from 0.48 ± 0.17 to 0.84 ± 0.11 at 1 year after intervention (P < .001), and patency rates at 1, 6, and 12 months after interventions were 100%, 80%, and 42%, respectively. CONCLUSIONS: A dual femoral-popliteal approach in the supine position is an alternative backup option after failed attempts at the antegrade approach for patients with proximal barriers in CTO or lesions with major extending collateral vessels.

[Assessment of external methods of traditional Chinese medicine in patients with chronic ulcer of the lower extremities: study protocol of a multicenter, randomized, parallel-group, prospective trial].

BACKGROUND: Chronic ulcer of the lower extremities amounts for a grave and serious problem for public health. Western medicine focuses on controlling infection, improving blood circulation, surgical debridement, skin grafting, etc, but there are bottlenecks in the treatment. Traditional Chinese medicine (TCM) has a long history and a legacy of sound clinical efficacy in this area. TCM has developed a unique, effective external theory, and a large number of topical prescriptions and external technology. Through this research, a safe and effective treatment protocol of TCM for chronic ulcer of the lower extremities can be formed. To this end, during China's "Eleventh Five-Year" Plan, special research committees and projects on TCM external treatments and external technologies were established. This study on ulcer of the lower extremities constitutes one of the major research topics. METHODS AND DESIGN: Clinical information of patients with chronic ulcer of the lower extremities will be first collected in a large, multicenter, epidemiological survey. Concurrently, a large multicenter, randomized, parallel-group, prospective study will be launched based on evidence-based medical principles to evaluate the efficacy and safety of external methods for removing carrion, dissolving stasis, reinforcing deficiency and promoting tissue regeneration. The evaluated indexes will include the wound healing percentage for primary outcome, wound healing time, wound healing rate, time and rate of removal of necrotic tissue, and TCM syndromes for secondary outcomes and routine blood test, routine urine test, liver and kidney function, blood mercury content and finally urine mercury content for adverse events. DISCUSSION: In this trial, the authors will evaluate the efficacy and safety of external methods for removing carrion, dissolving stasis, reinforcing deficiency and promoting tissue regeneration in cases of chronic ulcer of the lower extremities for standardizing external therapy of TCM for treatment of this condition, and establishing the clinical assessment system for TCM. TRIAL REGISTRATION NUMBER: The research program was registered in the Chinese Clinical Trial Registry in both English and Chinese in June 2011. REGISTRATION NUMBER: ChiCTR-TRC-11001365.

[Effects and action mechanisms of Buyang Huanwu Decoction in wound healing of chronic skin ulcers of rats].

OBJECTIVE: To explore the effects and action mechanisms of Buyang Huanwu Decoction, a compound traditional Chinese herbal medicine, in wound healing of chronic skin ulcers of rats. METHODS: A total of 54 male SD rats with back full-thickness skin lesion were used in this study. Except for the normal control group, the rats were injected with hydrocortisone for inducing chronic skin ulcers, and were randomly divided into untreated group and Buyang Huanwu Decoction group. The rate and the time of wound healing were observed. Immunohistochemical method and image analytical method were used to test the expression of vascular endothelial growth factor (VEGF) and microvessel count (MVC) in granulation tissue of chronic skin ulcers in the rats. RESULTS: The rate of wound healing was significantly lowered in the untreated group as compared with the normal control group (P<0.01, P<0.05), and the time of wound healing was obviously longer too (P<0.01). In the Buyang Huanwu Decoction group, the rate of wound healing was significantly higher than that in the untreated group (P<0.01), and the time of wound healing was obviously shorter than the latter's (P<0.01). In the untreated group, the expression of VEGF and MVC were significantly lower than those in the normal control group (P<0.01); the expression of VEGF and MVC were obviously increased in the Buyang Huanwu Decoction group as compared with those in the untreated group (P<0.01). CONCLUSION: Buyang Huanwu Decoction has the effect to promote the wound healing for chronic skin ulcers of rats by regulating the expression of VEGF in granulation tissue of chronic skin ulcers.

[Applying collateral disease theory to treat chronic dermal ulcer].

Collateral disease theory has been applied to investigate the pathogenesis of chronic dermal ulcer in traditional Chinese medicine. It is suggested that deficiency of vital qi is the pathological basis of chronic dermal ulcer with collaterals stagnation as the major pathological factor, and collaterals impairment by toxin evil is the main pathological change. The important principle in treatment of chronic dermal ulcer is established as strengthening the body resistance, dredging collaterals and removing toxins, and this enriched the theory of wound healing in traditional Chinese medicine, and has practical value.

[Therapy mainly for strengthening healthy energy to promote blood circulation in treating 112 diabetic patients with gangrene].

OBJECTIVE: To evaluate the effects of the therapy mainly for strengthening healthy energy to promote blood circulation in treating diabetic patients with gangrene. METHODS: A series of 112 diabetic patients with gangrene were investigated before and after treatment in the changes of wounds, clinical symptoms and quality of life. RESULTS: Fifty-eight cases were cured, 12 cases showed response, 36 cases improved, and 6 cases failure of treatment. The total obvious effect rate was 62.5% (70/112) and the amputation rate was 8.9% (10/112). The 104 diabetic cases of three-stage gangrene were classified into grade I, II and III. The total effect rates of the diabetic cases of grade I, II and III were 83.3% (30/36), 55.6% (35/63) and 20% (1/5), and the amputation rates were 0%, 12.7% (8/63), and 40% (2/5) respectively. After the treatment, the clinical symptoms, gangrene number, gangrene area and gangrene depth were obviously improved (P<0.05), and the quality of life was obviously improved (P<0.01), especially in physical condition, emotional well-being and therapeutic effects on patients (P<0.05). CONCLUSION: Strengthening healthy energy to promote blood circulation is effective in treating diabetic patients with gangrene.

Effect of runing II on the growth and metastasis of transplanted tumor in mammary cancer-bearing mice and its mechanism.

OBJECTIVE: To study the effect of Runing II (a Chinese herbal preparation for mammary cancer) on the growth and metastasis of transplanted tumor of mammary cancer MA-891-bearing TA2 mice and its mechanism. METHODS: The model of mammary cancer MA-891 cell strain transplanted tumor of TA2 mice with lung metastasis were developed to observe the effect of Runing II on the growth and metastasis of the transplanted tumor. The immunohistochemical method and image analysis were adopted to detect the levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), and micro-vessel count (MVC) and micro-vessel area (MVA). RESULTS: In the Runing II group, the tumor weight inhibition rate and the lung metastasis inhibition rate were 37.3% and 65.4% respectively, the tumor growth and lung metastasis were obviously inhibited; And the levels of VEGF and VEGFR, MVC and MVA were significantly decreased as compared with those in the tumor-bearing control group (P<0.05). CONCLUSION: The Chinese herbal preparation Running II can inhibit the metastasis of tumor through inhibiting the angiogenesis, and the mechanism is possibly related with down-regulation of VEGF and VEGFR expression.

[Effects of Chinese herbs for replenishing qi and resolving stagnation on hypoxia-inducible factor-1alpha and vascular endothelial growth factor in granulation tissue of skin ulcers in rats with diabetes].

OBJECTIVE: To explore the effects of Chinese herbs for replenishing qi and resolving stagnation on hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in granulation tissue of skin ulcers in rats with syndrome of blood stasis and qi deficiency. METHODS: Diabetic rats with back full-thickness skin lesion and syndrome of blood stasis and qi deficiency were divided in to five groups: untreated group, basic fibroblast growth factor (bFGF)-treated group, Yiqi Huayu Recipe (a recipe for replenishing qi and resolving stagnation)-treated group, Yiqi Recipe (a recipe for replenishing qi)-treated group and Huayu Recipe (a recipe for resolving stagnation)-treated group, and another eight normal rats served as normal control group. Immunohistochemical method and image analysis were used to test the expressions of HIF-1alpha and VEGF in granulation tissue of skin ulcers in rats with diabetes. RESULTS: In the untreated group, the expression of HIF-1alpha was significantly increased and the expression of VEGF was significantly decreased as compared with those in the normal control group (P<0.01). The expression of HIF-1alpha was obviously lower (P<0.01) and the expression of VEGF was significantly higher in the four drug treated groups as compared with those in the untreated group. In the Yiqi Huayu Recipe-treated group, the expression of HIF-1alpha was obviously lower than those in the bFGF-treated, Yiqi Recipe-treated and Huayu Recipe-treated groups (P<0.05 or P<0.01), and the expression of VEGF was significantly higher than that in the bFGF-treated group (P<0.01). CONCLUSION: Chinese herbs for replenishing qi and resolving stagnation can promote the wound healing in rats through reducing the expression of HIF-1alpha, accelerating the expression of VEGF in granulation tissue of skin ulcers in rats with diabetes and ameliorating the status of ischemia and hypoxia.

[Discussion of relationship between quality of life and clinical effect assessment of malignant tumor treated with traditional Chinese medicine].

Traditional Chinese Medicine (TCM) therapy is effective in treating malignant tumor. TCM therapy is a multi-way, multi-layer and multi-target integrated treatment characterized by "survival with tumor" and improvement of life quality. An ideal result of the TCM therapy for cancer should be a positive response of the patient with satisfactory quality of life (QOL) and longer survival time. So it is necessary to introduce the QOL, quantification of symptoms and signs and standardization of TCM syndromes to the objective, quantitative and standardized effect assessment of TCM therapy for cancer. A criterion for evaluating the effect of TCM therapy on tumors should be established, which reflects the characteristics and advantages of the TCM therapy, and meets the requirement of the developing effect assessment of modern medicine in cancer treatment. It is suggested that the treatment effect should be the sum of quality adjusted life years (QALYs) (equal to QOL multiplied by time of survival), syndrome remission rate and tumor remission rate. But the proportion of each of the three is variable, which has close relationships with the different tumor stages and corresponding treatments.