Efficacy of Spleen-and-Stomach-Tonifying, Yin-Fire-Purging, and Yang-Raising Decoction Derived from the Trimethylamine N-Oxide Metabolic Pathway of Intestinal Microbiota on Macrovascular Lesions Caused by Type 2 Diabetes Mellitus.

Objective: We aimed to analyze the mechanisms underlying spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction derived from the trimethylamine N-oxide (TMAO) metabolic pathway of intestinal microbiota in the treatment of macrovascular lesions caused by type 2 diabetes mellitus (T2DM). Methods: Hartley-guinea pigs were randomly divided into 3 groups-the blank, model, and intervention groups. The T2DM combined with atherosclerosis guinea pig models were established in the model and intervention groups. After successful modeling, spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction were administered intragastrically to the intervention group, while the same volume of normal saline was administered via gavage to the blank and model groups. After 6 weeks of continuous gavage, guinea pigs were sacrificed in all groups, the colon contents were obtained, and the diversity and structural differences of intestinal microbiota were analyzed via bioinformatics. Serum was collected to detect differences in lipids, TMAO, oxidative stress, and inflammation markers between groups. Results: Compared to the blank group, the species diversity of the intestinal microbiota in the model and intervention groups was significantly reduced. Based on the results of Analysis of Similarities and Multiple Response Permutation Procedure, the microbiota structure of the intervention group was closer to that of the blank group. After modeling, the blood lipid levels of guinea pigs increased significantly, and drug intervention significantly reduced the levels of TC, TG, and LDL-C (P < 0.05). TMAO expression was significantly increased after modeling (P < 0.05), while drug intervention reduced TMAO expression (P < 0.05). Compared to the model group, drug intervention significantly increased the concentrations of SOD while decreasing the concentrations of MDA, ICAM-1, VCAM-1, IL-6, and hs-CRP. Conclusion: Spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction can reduce the risk of macrovascular lesions in T2DM, and its mechanism may be associated with its ability to regulate the TMAO metabolic pathway of intestinal microbiota.

Clinical outcomes of toe amputation in patients with type 2 diabetes in Tianjin, China.

The aim of this study is to determine the predictors for reulceration, reamputation and mortality in patients with diabetes following toe amputation, and the impact of activities of daily living on clinical outcomes. This prospective cohort study included 245 patients who had undergone toe amputation (202 healing and 43 non-healing) and was followed for a 5-year period. Data regarding new foot ulceration, reamputation and mortality were recorded, and the patients' activities of daily living were evaluated. The rate of wound healing was 82·4%. The rate of follow-up in the healed group was 91·6%. In years 1, 3 and 5, the cumulative incidence of patients who developed a new foot ulcer was 27·3%, 57·2% and 76·4%, respectively, leading to reamputation in 12·5%, 22·3% and 47·1%, respectively. The cumulative mortality was 5·8%, 15·1% and 32·7% at 1, 3 and 5 years, respectively. Multivariate analysis showed that GHbA1c > 9% (75 mmol/mol) was identified as an independent predictor of impaired wound healing, reulceration and reamputation. An age of >70 years was identified as an independent predictor of reamputation, mortality and impairment of activities of daily living. Despite a satisfactory initial healing rate after the first toe amputation, with the extension course after the toe amputation, the long-term outcomes are not optimistic. In developing countries like China, taking measures to prevent reulceration and reamputation is very important for patients with diabetic foot minor amputations, especially following toe amputation.

Risk factors and gene type for infections of MRSA in diabetic foot patients in Tianjin, China.

The objective was to study risk factors and gene type of DF patients infected with MRSA. A total of 429 DF patients were recruited. The patients with S aureus infections were divided into MRSA and MSSA groups. MRSA were genotyped by SCCmec. pvl and lukE-lukD were detected. A total of 559 pathogens were isolated from them, with G+ bacteria firstly(59.0%), followed G- bacilli (37.7%) and true fungi (3.3%). The 3 most frequently isolated pathogens were S aureus (35.2%), S epidermidis (12.3%), and Pseudomonas aeruginosa (11.2%). SCCmec III MRSA and SCCmec IVa MRSA had the same antibacterial spectrum. mecA positive rate was 100%. lukE-lukD and pvl positive rates were 100% and 0%, respectively. 28 strains belonged to SCCmec III and the others belonged to SCCmec IVa. The G+ cocci were the main pathogens, S aureus and S epidermidis were predominant among them. Antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis and hypoproteinemia are risk factors for MRSA. SCCmec IVa is high in proportion to MRSA isolates, suggesting that CA-MRSA has become major pathogen of DF infection. All the MRSA were harboring lukE-lukD, which has been reported to present poor leucotoxin compared to pvl, and may be a response to atypical local inflammatory reaction in DF infection.

[Risk factors for infections of methicillin-resistant Staphylococci in diabetic foot patients].

OBJECTIVE: To examine the distribution patterns of pathogens isolated from the patients with diabetic foot ulcers and explore the risk factors for infections of methicillin-resistant S. aureus (MRSA) or methicillin-resistant S. epidermidis (MRSE). METHODS: A total of 388 diabetic-foot patients hospitalized at Tianjin Metabolic Diseases Hospital between January 2008 and June 2010 were recruited. The distribution profiles of pathogens isolated from diabetic foot ulcers were summarized. The patients with S. aureus infections were divided into MRSA and MSSA groups while those with S. epidermidis infections into MRSE and MSSE groups. The clinical features of these patients were compared between all groups. Logistic regression was employed to identify the risk factors for the MRSA/MRSE infections. RESULTS: A total of 362 pathogens were isolated from them. And the Gram-positive bacteria were the most predominant (57.2%, 207/362), followed by Gram-negative bacilli (39.2%, 142/362) and true fungi (3.6%, 13/362). The three most frequently isolated pathogens were S. aureus (27.1%), S. epidermidis (18.8%) and Pseudomonas aeruginosa (15.5%). Statistically significant differences existed in antibiotic usage in 6 months prior to hospitalization, course of ulcer, ulcer size, deep ulcer, osteomyelitis, hypertension, anemia, hypoproteinemia and erythrocyte sedimentation rate between the patients infected with MRSA and MSSA (P < 0.05). The MRSE infection was correlated with recurrent ulcer, osteomyelitis, hypoproteinemia, HbA1c and lower total serum protein (P < 0.05). Multiple Logistic regression analysis revealed that antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis, hypertension and hypoproteinemia were risk factors for the MRSA infection. And HbA1c was a risk factor for the MRSE infection. CONCLUSION: In the present study, the Gram-positive cocci are the main pathogens isolated from diabetic foot ulcers. And S. aureus and S. epidermidis are the most frequently isolated pathogens. Antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis, hypertension and hypoproteinemia are risk factors for the MRSA infection. And HbA1c is a risk factor for the MRSE infection.

[Research on the clinical features and effective factors of 249 diabetic patients with deep foot infection].

OBJECTIVE: 249 diabetic patients with deep foot infection were retrospectively studied. Their clinical features and effective factors related to wound healing were analyzed. METHODS: 249 patients team (physician, surgeon and diabetes-specific nurse) were divided into 3 groups. Group A: patients healed without amputation (n = 107), group B: patients healed after amputation (n = 114), and group C: patients didn't heal after amputation. All patients' clinical features, lab examinations and foot wound features were compared. RESULTS: The group A patient were (59 +/- 12) years old, significantly younger than the group B (67 +/- 11, P < 0.01). Hypersensitive C reactive protein (hs-CRP, 18 +/- 5 mg/L) and plasma albumin (32 +/- 7 g/L) of group A were significantly higher than those of group B (13 +/- 5 mg/L and 29 +/- 5 g/L, respectively, P < 0.01). The duration of diabetes mellitus of group B (17 +/- 11) year was significantly longer than that of group A (10 +/- 6 year, P < 0.05). The possibility of probing bone, purulent secretion, necrosis, bone exposure, cacosmia, edema and critical limb ischemia of group B were more frequent (P < 0.01 or P < 0.05) compared to group A. The age of group B (67 +/- 11) are younger than that of group C (72 +/- 9, P < 0.05). In group B, temperature (38.1 +/- 1.1) degrees C, white blood cell (WBC) count (10 +/- 3) x 10(9)/L and hs-CRP (13 +/- 5) mg/L were higher than those of group C (37.4 +/- 0.8 degrees C, 8 +/- 2 x 10(9)/L and 7 +/- 6 mg/L, respectively, all P < 0.05). Critical limb ischemia of group B (37%) was more frequent than that of group A (7%, P < 0.05), but less frequent than that of group C (77%, P < 0.01). hs-CRP and plasma albumin were protective factors for wound healing. Age, the possibility of probing bone, purulent secretion, necrosis, bone exposure, cacosmia, edema and critical limb ischemia were risk factors for wound healing. CONCLUSION: diabetic patients with deep foot infection are difficult to be diagnosed in early stage since they often have no significant clinical syndrome such as fever, redness, swelling and pain, and their WBC count does not increase. Though multidisciplinary team manages these patients, more than half of them need amputation. Wound healing in the patients is related to multiple factors, including age, duration of diabetes mellitus, hs-CRP, plasma albumin, WBC count, level of limb ischemia and wound features.