Protective effects of Wuwei Xiaodu Drink against chronic osteomyelitis through Foxp3+CD25+CD4+ Treg cells via the IL-2/STAT5 signaling pathway / 中国天然药物

To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink (WWXDD) in inhibiting chronic osteomyelitis via regulatory T cells signaling. The effective constitutes of WWXDD and osteomyelitis related genes were screened. Target proteins were cross-validated using the Venny database. GO function and KEGG pathway analysis were performed for target proteins, while pharmacological network was constructed. The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA. The expression of CTLA-4 and Foxp3 mRNA and STAT5, p-STAT5, CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot, respectively. FACS was used to analyze the percentages of cells. A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes. Inflammation-related genes, including IL-6, TNFα, IL-1β and IL-2 showed high connection degree in the drug-compound-disease-target network. GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways, immune related pathways and chemokine signaling pathway. Furthermore, the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD. Meanwhile, the concentrations of IL-2 and CD4+CD25+Foxp3 Treg percentages together with the levels of p-STAT5, CTLA-4 and Foxp3 were also down-regulated. Furthermore, IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2, IL-10, TGF-β1, Foxp3, CTLA4 and STAT5. In addition, a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4. WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression. Our results bring a new solution for chronic osteomyelitis.

Surgical treatment of traumatic osteomyelitis of extremities with MRSA infection / 中国骨伤

OBJECTIVE@#To summarize and discuss the clinical efficacy and application value of intravenous drip of linezolid combined with local targeted sustained-release of vancomycin in the treatment of traumatic osteomyelitis of extremities infected with MRSA.@*METHODS@#Thirty patients with traumatic osteomyelitis of extremities infected by MRSA from March 2015 to March 2017 were analyzed retrospectively, including 21 males and 9 females; aged 25 to 64 years old, with an average age of(47.94± 6.23) years old;the course of disease ranged from 9 to 23 months, with an average of (15.68±6.23) months. The lesions were located in tibia in 18 cases and calcaneus in 12 cases. The causes of injury were fall injury in 12 cases, trafficaccident injury in 9 cases and fall injury in 9 cases. There were 22 patients with closed fractures and 8 patients with open fractures. There were 13 cases of internal fixation. Twenty-two patients had sinustract, 8 patients had soft tissue defect with bone and internal fixation exposure, soft tissue defect area ranged from 2.0 cm × 3.0 cm to 8.2 cm × 12.3 cm;10 patients had bone defect, defect area ranged from 0.5 to 3.4 cm;bacterial culture of sinus tract or wound secretion in all patients was MRSA. On the basis of thorough debridement, calcium sulfate artificial bone loaded with vancomycin was implanted in the lesion, and linezolid and glucose injection was given intravenously during the perioperative period. The patients were followed up regularly according to the time of antibiotic use, blood routine, erythrocyte sedimentation rate, high-sensitivity C-reactive protein, liver and kidney function and other related laboratory indexes, X-ray, CT and other imaging examinations, bone healing, flap survival, joint function and McKee's osteomyelitis cure criteria.@*RESULTS@#All the patients were followed up, and the duration ranged from 3 to 6 years, with a mean of (4.23±0.76) years. No recurrence of osteomyelitis occurred. Fracture healing, infection control, wound healing and functional recovery were achieved.@*CONCLUSION@#Intravenous drip of linezolid combined with local targeted sustained-release of vancomycin for the treatment of MRSA infected traumatic osteomyelitis in limbs have significant effects and low recurrence rates.