Chalcone derivatives ameliorate lipopolysaccharide-induced acute lung injury and inflammation by targeting MD2.

Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are known as the common causes of respiratory failure in critically ill patients. Myeloid differentiation 2 (MD2), a co-receptor of toll like receptor 4 (TLR4), plays an important role in LPS-induced ALI in mice. Since MD2 inhibition by pharmacological inhibitors or gene knockout significantly attenuates ALI in animal models, MD2 has become an attractive target for the treatment of ALI. In this study we identified two chalcone-derived compounds, 7w and 7x, as new MD2 inhibitors, and investigated the therapeutic effects of 7x and 7w in LPS-induced ALI mouse model. In molecular docking analysis we found that 7w and 7x, formed pi-pi stacking interactions with Phe151 residue of the MD2 protein. The direct binding was confirmed by surface plasmon resonance analysis (with KD value of 96.2 and 31.2 µM, respectively) and by bis-ANS displacement assay. 7w and 7x (2.5, 10 µM) also dose-dependently inhibited the interaction between lipopolysaccharide (LPS) and rhMD2 and LPS-MD2-TLR4 complex formation. In mouse peritoneal macrophages, 7w and 7x (1.25-10 µM) dose-dependently inhibited LPS-induced inflammatory responses, MAPKs (JNK, ERK and P38) phosphorylation as well as NF-κB activation. Finally, oral administration of 7w or 7x (10 mg ·kg-1 per day, for 7 days prior LPS challenge) in ALI mouse model significantly alleviated LPS-induced lung injury, pulmonary edema, lung permeability, inflammatory cells infiltration, inflammatory cytokines expression and MD2/TLR4 complex formation. In summary, we identify 7w and 7x as new MD2 inhibitors to inhibit inflammatory response both in vitro and in vivo, proving the therapeutic potential of 7w and 7x for ALI and inflammatory diseases.

Transoral anterior release, odontoid partial resection, and reduction with posterior fusion for the treatment of irreducible atlantoaxial dislocation caused by odontoid fracture malunion.

PURPOSE: Several techniques have been introduced to manage irreducible atlantoaxial dislocation (IAAD). However, no study has reported the surgical method for the management of IAAD caused by odontoid fracture malunion. This study aimed to introduce a surgical method of transoral anterior release, odontoid partial resection, and reduction with sequential posterior fusion for the treatment of IAAD caused by odontoid fracture malunion. We also evaluated the clinical efficacy of this surgery. METHODS: This study included seven cases of IAAD caused by odontoid fracture malunion, collected from January 2008 to January 2011. Anterior atlantoaxial release was performed through anterior transoral approach, followed by partial resection of the odontoid process. C1-C2 were then fixed through pedicle screws and rods, and then fused posteriorly by single stage. Neurologic status was evaluated using the Japanese Orthopaedic Association (JOA) scoring system. RESULTS: All seven patients had complete release, and satisfactory reduction. Bony fusion was seen in all patients postoperatively. The patients were followed up for an average of 19.6 months (ranged from 9 to 36 months). The average of patients JOA scores at the final follow-up was significantly higher than that of their preoperative scores. Furthermore, the average improvement in neurological function was 87.4 %. No screw loosening, implant migration or implant failures, atlantoaxial redislocation, or signs of instability were observed in any of the patients during the follow-up period. CONCLUSIONS: Transoral anterior release, odontoid partial resection, and reduction combined with posterior fusion are effective, reliable, and safe procedures for the treatment of IAAD caused by odontoid fracture malunion.

Avulsion fracture of the anterior superior iliac crest following autograft for anterior lumbar fusion: case report and literature review.

Avulsion fracture of the anterior superior iliac crest (ASIC) following autogenous bone grafting for anterior lumbar fusion (ALF) is an extremely rare complication. We describe a very rare case of avulsion fracture of the ASIC following autograft for ALF in a revision surgery for treating lumbar tuberculosis. A 68-year-old woman with lumbar tuberculosis underwent posterior debridement and posterior iliac crest bone graft fusion; however, her lumbar tuberculosis recurred 9 months after surgery. She then underwent a lumbar revision surgery, including removal of the posterior instrumentation and debridement, followed by anterior L2 corpectomy, debridement, anterior left iliac crest bone graft fusion, and internal fixation. When walking for the first time on postoperative day 3, she experienced a sharp, sudden-onset pain in the anterior iliac crest harvest area. X-ray revealed an avulsion fracture of the ASIC. Considering her failure to respond to conservative treatment for one week and large displacement of the fracture ends, an open reduction and internal fixation surgery was scheduled. Her pain symptoms were significantly relieved after the operation. Although rare, fracture of the ASIC following autograft for ALF should not be ignored. Fracture of the ASIC is usually treated conservatively. Additional surgical treatment is required only when intractable pain fails to respond to conservative treatment or when there is a large displacement of fracture ends that are not expected to heal spontaneously.

Bioprinting for bone tissue engineering.

The shape transformation characteristics of four-dimensional (4D)-printed bone structures can meet the individual bone regeneration needs, while their structure can be programmed to cross-link or reassemble by stimulating responsive materials. At the same time, it can be used to design vascularized bone structures that help establish a bionic microenvironment, thus influencing cellular behavior and enhancing stem cell differentiation in the postprinting phase. These developments significantly improve conventional three-dimensional (3D)-printed bone structures with enhanced functional adaptability, providing theoretical support to fabricate bone structures to adapt to defective areas dynamically. The printing inks used are stimulus-responsive materials that enable spatiotemporal distribution, maintenance of bioactivity and cellular release for bone, vascular and neural tissue regeneration. This paper discusses the limitations of current bone defect therapies, 4D printing materials used to stimulate bone tissue engineering (e.g., hydrogels), the printing process, the printing classification and their value for clinical applications. We focus on summarizing the technical challenges faced to provide novel therapeutic implications for bone defect repair.

Effects of Tianxiangdan Granule treatment on atherosclerosis via NF­κB and p38 MAPK signaling pathways.

The present study aimed to determine the effects of Tianxiangdan Granule on nuclear factor (NF)-κB p65 and p38 mitogen­activated protein kinase (MAPK) inflammatory signaling pathways, and explored the possible mechanism underlying the effects of Tianxiangdan Granule on prevention and treatment of atherosclerosis. A total of 48 apolipoprotein E­/­ mice (age, 8 weeks) were selected and divided into two groups: The normal control group (n=12) and the modeling group (n=36). In the modeling group, mice were fed a high­fat diet and were maintained in an artificial climate box, in order to stimulate the climate and eating habit characteristics of Xinjiang. Every morning, ApoE­/­ mice in the modeling group were placed in the artificial climate box at 10:00 am and were taken out at 09:00 pm and placed back in the room temperature environment. The temperature of the artificial climate box was set at 6±2˚C, relative humidity was controlled at 25­32.8% and the light­dark cycle was 12 h/day. The purpose of this method was to establish the Huizhuo Tanzu type atherosclerosis model. Following successful generation of the model, mice in the modeling group were randomly divided into three groups: Model group (n=10), Tianxiangdan group (n=10) and atorvastatin group (n=10). After 12 weeks, mice were sacrificed and the serum levels of interleukin (IL)­1ß and tumor necrosis factor (TNF)­α in each group were detected. Furthermore, the expression levels of NF­κB p65 and p38 MAPK in aortic tissue were detected. The results indicated that the concentrations of IL­1ß and TNF­α were significantly higher in mice in the model group compared with in the normal control group (P<0.01), whereas the concentrations of IL­1ß and TNF­α were lower in the Tianxiangdan and atorvastatin groups compared with in the model group (P<0.01). Furthermore, the protein expression levels of phosphorylated (p)­NF­κB p65 and p­p38 MAPK protein were higher in aortic tissues from the model group compared with in the normal control group (P<0.01), p­NF­κB p65 and p­p38 MAPK protein expression was reduced in the atorvastatin and Tianxiangdan groups compared with in the model group. The present study indicated that the mechanism underlying the effects of Tianxiangdan Granule on the prevention and treatment of atherosclerosis may be as follows: Tianxiangdan Granule may decrease the expression of the inflammatory cytokines IL­1ß and TNF­α, and suppress activation of the NF­κB p65 and p38 MAPK signaling pathways.

[Effects of slow/controlled release urea on annual CH4 and N2O emissions in paddy field.] / 缓/æŽ§é‡Šå°¿ç´ å¯¹ç¨»ç”°å‘¨å¹´CH4和N2O排放的影响.

Present study examined the influence of different types of slow/controlled release urea on rice yield and annual greenhouse gas emissions in a paddy field, and assessed the greenhouse gas intensity (GHGI, equivalent to global warming potential GWP/rice yield). The results indicated that the optimized fertilization (OPT) treatment recorded the similar yield with reduced nitrogen fertilizer (21.4%) supply compared with the farmers' fertilizer practice (FFP) treatment, and decreased the annual emissions of CH4 (12.6%) and N2O (12.5%) during the rice season, and N2O emission (33.3%) during the fallow period. Application of controlled release urea (CRU) reduced CH4 emission by 28.9% during the rice-growing season with respect to OPT treatment, and showed negligible CH4 emission during the fallow season. However, nitrification inhibitor (DMPP) treatment was found to reduce the CH4 emissions by 41.6% and 76.9%, and N2O emissions by 85.7% and 6.5%, during the rice growing season and fallow season, respectively, compared with OPT treatment. In the fallow season, the N2O emissions accounted for 76.8%-94.9% of annual N2O emissions, which was clearly a key point for evaluation of greenhouse gas emissions in paddy. The average values of GHGI in OPT, CRU and DMPP treatments were 0.50, 0.41 and 0.33 kg·kg-1, respectively. Considering the benefits of higher rice yield and lower annual greenhouse gas emissions, combined application of urea and nitrification inhibitor could be the best combination in paddy fields.

[Characteristic and surgical treatment of cervicothoracic spine fracture].

OBJECTIVE: To discuss the clinical characteristic and surgical treatment of cervicothoracic spine fracture complicated with spine cord injury. METHODS: Thirty-eight patients with cervicothoracic fracture and spine cord injury were retrospectively analyzed from January 1998 to January 2007. There were 29 males and 9 females with an average age of 36.4 years ranging from 18 to 58 years. All patient suffered from pain and limitation of motion on cervicothoracic junction. According to American Spinal Injury Association (ASIA) grades, 4 cases were in grade A, 13 cases in grade B, 10 cases in grade C, 7 cases in grade D and 4 cases in grade E. All patients were treated with anterior decompressed, bone graft and Zephir plate fixation in cervicothoracic spine. RESULTS: All patients were followed up for 1 to 10 years, the mean followed up time was 4.5 years. And all patients got complete bone fusion within 4 to 6 months postoperatively. There were no pull-out and breakage of screws or plates. Spinal cord functional recovery improved on average 3.8 degree according AISA standard. Two patients appeared transient hoarse voice after surgery, the symptoms were alleviated from 3 to 6 months after operation. Seven patients were complicated with Horner syndrome preoperatively, and the symptoms were disappeared after operation. CONCLUSION: The clinical situation of cervicothoracic spine fracture with spine cord injury is complicated. And anterior decompressed, bone graft and internal fixation performed on cervicothoracic spine fracture can achieve an efficient and safe clinical outcome.