OBJECTIVE To investigate the effects of loganin on inflammatory response and intestinal barrier damage in septic rats by regulating the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase 1 （ROCK1） signaling pathway. METHODS A sepsis rat model was established by cecal ligation and puncture， and randomly divided into sepsis group， loganin low-dose group （50 mg/kg loganin， gavage）， loganin high-dose group （200 mg/kg loganin， gavage）， positive control group （0.2 mg/kg atorvastatin， intraperitoneal injection）， and loganin high-dose + lysophosphatidic acid （LPA） group （200 mg/kg loganin gavage and intraperitoneal injection of 10 mg/kg RohA activator LPA）. An additional sham surgery group was established. Each group consisted of 10 rats， and medications were administered once every 6 hours for 4 times. After 24 hours of the last intervention， the levels of serum inflammatory factors interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β were detected. The pathological changes of ileal tissue were observed and Chiu’s intestinal mucosal injury score was also performed. The levels of intestinal function-lactate dehydrogenase （D-lactate）， D-amino acid oxidase （DAO） and endotoxin， the percentages of zonula occludens-1 protein （ZO-1） and Occludin positive staining area， as well as protein expressions of RhoA， and ROCK1 were all detected. com RESULTS Compared with the sepsis group， the percentages of ZO-1 and Occludin positive areas increased significantly in loganin low-dose and high-dose groups； while the levels of IL-6， TNF-α， IL-1β， DAO， D-lactate and endotoxin， Chiu’s intestinal mucosal injury score as well as protein expressions of RhoA and ROCK1 decreased significantly （P＜0.05）； the destruction of rat ileal tissue was alleviated， and tissue edema and inflammatory infiltration were significantly reduced； moreover， the improvement effect in loganin high-dose group was superior to that in loganin low-dose group （P＜0.05）. Compared with loganin high-dose group， RhoA activator LPA reversed the trend of changes in the above indicators （P＜0.05）. CONCLUSIONS Loganin can alleviate inflammatory response and intestinal barrier damage in septic rats， the mechanism of which may be associated with inhibiting RhoA/ROCK1 signaling pathway.

The difficulty in the treatment of diabetic foot lies in the high rate of recurrence and difficulty in eradicating the disease, and the results of both systemic basic treatment and local surgical treatment are not ideal. In recent years, domestic scholars have applied tibial transverse transport for the treatment of diabetic foot. Tibial transverse transport is suitable for the treatment of severe diabetic foot with a good blood supply of the large and middle arteries. It has the advantages of high healing rate and low recurrence rate, and can effectively reduce the mortality and amputation rate of patients. However, postoperative complications such as tibial osteotomy fracture, pin tract infection, skin necrosis at osteotomy area, tibial deformity and osteomyelitis should be paid attention to. Domestic scholars have improved the operation of tibial transverse bone transport in terms of reducing the surgical incision, osteotomy area, and preserving the blood supply of the osteotomy site. The modified double bone flap transverse tibial bone transport and "door" shaped window technique have been derived, and related surgical instruments have also been improved in the direction of precision. At present, the research on the mechanism of tibial transverse transport in the treatment of diabetic foot mainly focuses on promoting the reconstruction of macrophage polarization balance, stem cell mobilization and angiogenesis. After tibial transverse transport, the polarization of macrophages to classical activated type was decreased, and the polarization of selective activated type was increased. The two mechanisms promoted each other to reconstruct the polarization balance of macrophages. Bone transport activated SDF-1/CXCR4/PI3K/AKT and Wnt signaling pathways to induce stem cell mobilization. At the same time, it stimulates the release of angiogenic factors, activation of endothelial progenitor cells and Ras/Raf/MEK/ERK signaling pathways to promote angiogenesis and ultimately promote the healing of diabetic foot ulcers.

The difficulty in the treatment of diabetic foot lies in the high rate of recurrence and difficulty in eradicating the disease, and the results of both systemic basic treatment and local surgical treatment are not ideal. In recent years, domestic scholars have applied tibial transverse transport for the treatment of diabetic foot. Tibial transverse transport is suitable for the treatment of severe diabetic foot with a good blood supply of the large and middle arteries. It has the advantages of high healing rate and low recurrence rate, and can effectively reduce the mortality and amputation rate of patients. However, postoperative complications such as tibial osteotomy fracture, pin tract infection, skin necrosis at osteotomy area, tibial deformity and osteomyelitis should be paid attention to. Domestic scholars have improved the operation of tibial transverse bone transport in terms of reducing the surgical incision, osteotomy area, and preserving the blood supply of the osteotomy site. The modified double bone flap transverse tibial bone transport and "door" shaped window technique have been derived, and related surgical instruments have also been improved in the direction of precision. At present, the research on the mechanism of tibial transverse transport in the treatment of diabetic foot mainly focuses on promoting the reconstruction of macrophage polarization balance, stem cell mobilization and angiogenesis. After tibial transverse transport, the polarization of macrophages to classical activated type was decreased, and the polarization of selective activated type was increased. The two mechanisms promoted each other to reconstruct the polarization balance of macrophages. Bone transport activated SDF-1/CXCR4/PI3K/AKT and Wnt signaling pathways to induce stem cell mobilization. At the same time, it stimulates the release of angiogenic factors, activation of endothelial progenitor cells and Ras/Raf/MEK/ERK signaling pathways to promote angiogenesis and ultimately promote the healing of diabetic foot ulcers.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg^-1) for five days, followed by BBP (50, 100, and 200 mg·kg^-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.
Humans ; Mice ; Rats ; Animals ; Aged ; Middle Aged ; Parkinson Disease/pathology* ; Astrocytes/pathology* ; Powders/therapeutic use* ; Ursidae/metabolism* ; NF-kappa B/metabolism* ; Neuroinflammatory Diseases ; Neurodegenerative Diseases/metabolism* ; Cyclooxygenase 2/metabolism* ; Lipopolysaccharides/pharmacology* ; Bile ; Mice, Inbred C57BL ; Microglia ; Disease Models, Animal

Objective To investigate the application and effect of hydrocortisone during perioperation of retroperitoneum laparoscopic surgery for Cushing's syndrome.Methods Data of 56 cases of Cushings's syndrome treated by hormone replacement therapy of hydrocortisone were retrospectively analyzed .The hormone replacement therapy was as the following:no hormone before surgery, intravenous drip of hydrocortisone during and the 1st and 2nd day after surgery, oral intake of hydrocortisone from the 2nd after surgery.Clinical symptoms were observed and plasma,24h urine cortisol levels were intermittently measured after the surgery to evaluate the effects of treatment . Results 2 cases had slight cortical dysfunction symptoms, then back to normal after receiving larger dose of hydro-cortisone.6 cases had blood cortisol levels below the normal range , but they did not have cortical dysfunction symp-toms, and at the same time their 24h urine cortisol levels were normal .Urine cortisol concentration significantly de-creased on the 7th day after surgery, and had significant difference compared with that before surgery .Plasma cortisol concentration significantly decreased on the 6th, 7th day after surgery, and had significant difference compared with that before operation.All the cases recovered well.Conclusion Perioperative hydrocortisone replacement in retroper-itoneum laparoscopic surgery for Cushing's syndrome is safe.