Current opinions on the mechanism, classification, imaging diagnosis and treatment of post-traumatic osteomyelitis.

Post-traumatic osteomyelitis (PTO) is a worldwide problem in the field of orthopaedic trauma. So far, there is no ideal treatment or consensus-based gold standard for its management. This paper reviews the representative literature focusing on PTO, mainly from the following four aspects: (1) the pathophysiological mechanism of PTO and the interaction mechanism between bacteria and the body, including fracture stress, different components of internal fixation devices, immune response, occurrence and development mechanisms of inflammation in PTO, as well as the occurrence and development mechanisms of PTO in skeletal system; (2) clinical classification, mainly the etiological classification, histological classification, anatomical classification and the newly proposed new classifications (a brief analysis of their scope and limitations); (3) imaging diagnosis, including non-invasive examination and invasive examination (this paper discusses their advantages and disadvantages respectively, and briefly compares the sensitivity and effectiveness of the current examinations); and (4) strategies, including antibiotic administration, surgical choices and other treatment programs. Based on the above-mentioned four aspects, we try to put forward some noteworthy sections, in order to make the existing opinions more specific.

Ulk1 over-expression in human gastric cancer is correlated with patients' T classification and cancer relapse.

Ulk1 is a key autophagy protein. Here, we tested expression and potential function of Ulk1 in human gastric cancer. Ulk1 mRNA and protein were significantly elevated in multiple fresh human gastric cancer tissues. Its level was relatively low in surrounding normal epithelial tissues. Ulk1 over-expression was also observed in several gastric cancer cell lines (AGS, HGC-27, and SNU601). Remarkably, Ulk1 knockdown by targeted-shRNA inhibited AGS gastric cancer cell survival and proliferation. On the other hand, exogenous Ulk1 over-expression could further promote AGS cell survival and proliferation. Immunohistochemistry (IHC) staining assay of 145 paraffin-embedded gastric cancer tissues showed that Ulk1 was over-expressed in majority (114 out of 145) of gastric cancer tissues. Importantly, high Ulk1 expression in gastric cancer was correlated with patients' T classification and cancer relapse. Together, we demonstrate that Ulk1 over-expression in human gastric cancer is pro-survival. Its over-expression is associated with patients' T classification and cancer relapse.

Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury.

Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats.

Gabapentin Effects on PKC-ERK1/2 Signaling in the Spinal Cord of Rats with Formalin-Induced Visceral Inflammatory Pain.

Currently, the clinical management of visceral pain remains unsatisfactory for many patients suffering from this disease. While preliminary animal studies have suggested the effectiveness of gabapentin in successfully treating visceral pain, the mechanism underlying its analgesic effect remains unclear. Evidence from other studies has demonstrated the involvement of protein kinase C (PKC) and extracellular signal-regulated kinase1/2 (ERK1/2) in the pathogenesis of visceral inflammatory pain. In this study, we tested the hypothesis that gabapentin produces analgesia for visceral inflammatory pain through its inhibitory effect on the PKC-ERK1/2 signaling pathway. Intracolonic injections of formalin were performed in rats to produce colitis pain. Our results showed that visceral pain behaviors in these rats decreased after intraperitoneal injection of gabapentin. These behaviors were also reduced by intrathecal injections of the PKC inhibitor, H-7, and the ERK1/2 inhibitor, PD98059. Neuronal firing of wide dynamic range neurons in L6-S1 of the rat spinal cord dorsal horn were significantly increased after intracolonic injection of formalin. This increased firing rate was inhibited by intraperitoneal injection of gabapentin and both the individual and combined intrathecal application of H-7 and PD98059. Western blot analysis also revealed that PKC membrane translocation and ERK1/2 phosphorylation increased significantly following formalin injection, confirming the recruitment of PKC and ERK1/2 during visceral inflammatory pain. These effects were also significantly reduced by intraperitoneal injection of gabapentin. Therefore, we concluded that the analgesic effect of gabapentin on visceral inflammatory pain is mediated through suppression of PKC and ERK1/2 signaling pathways. Furthermore, we found that the PKC inhibitor, H-7, significantly diminished ERK1/2 phosphorylation levels, implicating the involvement of PKC and ERK1/2 in the same signaling pathway. Thus, our results suggest a novel mechanism of gabapentin-mediated analgesia for visceral inflammatory pain through a PKC-ERK1/2 signaling pathway that may be a future therapeutic target for the treatment of visceral inflammatory pain.

[Pathomorphological observation of the hypertrophic scar induced by injury to conical structure in female red Duroc pig].

UNLABELLED: To further explore the relationship between hypertrophic scar and injury to conical structure of skin and the pathogenesis of hypertrophic scar, and to reproduce an optimal animal model of hypertrophic scar. METHODS: The back of two FRDP pigs were shaved, and a piece of normal skin was harvested for the observation of conical structure of skin. Skin wounds with depth of 0.38 mm, 0.76 mm, 1.14 mm and 1.52 mm, respectively, were created by gas-driven dermatome. Eight wounds measuring 7.0 cm x 7.0 cm were created on each pig. The wounds were divided into 4 groups according to the wound depth with 4 wounds in each group, i.e. 0.38 mm group, 0.76 mm group, 1.14 mm group and 1.52 mm group. The 0.38 mm and 0.76 mm groups were designated as superficial wound groups and 1.14 mm and 1.52 mm groups as deep wound groups. The wounds were allowed to heal without treatment. Tissue samples from the wound were harvested on 0, 10, 30, 60, 90 and 150 post injury day (PID) , and they were sectioned for HE staining and staining for elastic fibers (VVG). The wound healing and the scar formation were observed with naked eye. The skin conical structures in normal and injured skin were also observed. The morphology of hypertrophic scar was observed, and the thickness of the scar tissue was determined and scored. RESULTS: The wounds in superficial wound groups healed within 3 weeks with flat surface without scar formation. The wounds in deep wound groups healed later than 4 weeks with thick, hairless, hard in texture, with depigmentation or pigmentation, finally forming contracture. The skin conical structure could be found on the back of FRDP with HE and VVG staining, and it was similar to that of human in terms of the structure. In superficial wound groups, the upper part of the skin conical structure was injured, but fat fornix and glands were intact. In deep wound groups, the lower part of the skin cone, together with the fat fornix and gland were all injured. On the 150th post injury day, the histological picture of the tissue in superficial wound groups was similar to that of normal skin. But the skin conical structure could not be found in deep wound groups, and the wounds were filled by a large accumulation of disarrayed and irregularly arranged collagen fibers. With passage of time, the scar became thicker and thicker, and the scar hypertrophy reached the zenith in 150th PID. CONCLUSION: The injury of skin conical structure can lead to the formation of hypertrophic scar. FRDP can be used to reproduce and ideal model of hypertrophic scar.

Effects of various muscarinic ligands on M2AChR-Gi1alpha fusion protein expressed in Sf9 insect cells.

AIM: To generate M2AChR-Gi1alpha fusion protein in baculovirus-Sf9 cells system and detect the effects of various muscarinic ligands and magnesium ion on the interaction of fused M2AChR and Gi1alpha. METHODS: M2AChR-Gi1alpha fused DNA was generated in a two step polymerase chain reaction (PCR) and then expressed in Sf9 cells to produce fusion protein. [3H] L-quinuclidinyl benzilate (QNB) and 35S GTPgammaS binding experiments were performed to study the function of M2AChR-Gi1alpha fusion protein. RESULTS: The expression level of M2AChR-Gi1alpha was (20.12 +/- 0.14) nmol/g protein. The affinity of GDP to Gi1alpha partner changed in the presence of different muscarinic ligands. IC50 values (95 % confidence limit) of GDP in the presence of acetylcholine (ACh), carbamylcholine, (4-hydroxy-2-butynyl)-1-trimethylammonium-m-chloro-carbanilate chloride (McN-A-343), pilocarpine, and atropine were 178 (148 - 214) micromol/L, 158 (126 - 199) micromol/L, 66 (56 - 78) micromol/L, 62 (55 -7 2) micromol/L, and 5.0 (4.6 - 5.5) micromol/L, respectively, and that in the absence of muscarinic ligand was 15.9 (14.3 - 17.6) micromol/L. Apparent affinity for GDP in the presence of carbamylcholine was markedly decreased with increasing MgCl2 concentrations, although the apparent affinity in the presence of atropine was not affected. CONCLUSION: The M2AChR-Gi1alpha fusion protein has the pharmacological specificity of M2 receptor and the efficient signaling of the two partners. Affinity of GDP to ligand-bound fusion protein represents the species of muscarinic ligands. Mg2+ is necessary for the action of M2AChR on Gi1alpha.