Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway

Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

Tibiocalcaneal arthrodesis via bone transport technique for traumatic talus infection or defect / 中华创伤杂志

Objective To investigate the clinical efficacy of tibiocalcaneal arthrodesis using bone transport technique in the treatment of traumatic talus infection or loss. Methods A retrospective case series study was conducted to analyze the clinical data of 15 patients with talus infection or loss admitted to the provincial hospital affiliated to Shandong University from June 2011 to October 2017. There were 13 males and two females, aged from 19 to 47 years, with an average age of 27 years. Thirteen patients had talus infection and two patients had talus loss. All patients underwent tibiocalcaneal fusion with external fixator using bone transport technique, including four patients treated with annular external fixator and 11 with unilateral external fixator. Six patients with severe infection underwent debridement at stage I and osteotomy at stage II, and the other nine underwent debridement and osteotomy at the same time. The length of new bone, the fixation time of external fixator and complications were recorded. The American Orthopedic Foot and Ankle Society ( AOFAS ) score was used to evaluate the efficacy. Results All patients were followed up for 18-35 months, with an average of 26 months. The length of new bone in proximal tibial osteotomy area was 5-16 cm, with an average of 9 cm. The external fixators were removed after bone healing at docking site and maturation of new bone. The fixation time of external fixator ranged from 13 to 27 months, with an average of 18 months. No complications such as needle breakage, recurrence of infection and calcaneal varus occurred, and the length of both lower limbs was equal. AOFAS score was increased from preoperative (42. 0 ± 3. 6)points (31-55 points) to (76. 0 ± 4. 2)points (69-86 points ) at the last follow-up. Conclusion Tibiocalcaneal arthrodesis using bone transport technique is proved to be effective in treating traumatic talus infection or loss, which can repair the bone defect after debridement, improve the ankle-hindfoot function and improve the quality of life.