BACKGROUNDThe renoprotective mechanisms of adenosine monophosphate (AMP)-activated protein kinase (AMPK) agonist - metformin have not been stated clearly. We hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines. The aim of this study was to observe the effects of metformin on expression of nuclear factor-κB (NF-κB), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta 1 (TGF-β1) induced by high glucose (HG) in cultured rat glomerular mesangial cells (MCs).

METHODSMCs were cultured in the medium with normal concentration glucose (group NG, 5.6 mmol/L), high concentration glucose (group HG, 25 mmol/L) and different concentrations of metformin (group M1, M2, M3). After 48-hour exposure, the supernatants and MCs were collected. The expression of NF-κB, MCP-1, ICAM-1, and TGF-β1 mRNA was analyzed by real time polymerase chain reaction. Western blotting was used to detect the expression of AMPK, phospho-Thr-172 AMPK (p-AMPK), NF-κB p65, MCP-1, ICAM-1, and TGF-β1 protein.

RESULTSAfter stimulated by HG, the expression of NF-κB, MCP-1, ICAM-1, TGF-β1 mRNA and protein of MCs in group HG increased significantly compared with group NG (P < 0.05). Both genes and protein expression of NF-κB, MCP-1, ICAM-1, TGF-β1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner (P < 0.05). The expression of p-AMPK increased with the rising of metformin concentration, presenting the opposite trend, while the level of total-AMPK protein was unchanged with exposure to HG or metformin. Conlusion Metformin can suppress the expression of NF-κB, MCP-1, ICAM-1 and TGF-β1 of glomerular MCs induced by high glucose via AMPK activation, which may partly contribute to its reno-protection.

AMP-Activated Protein Kinases ; metabolism ; Animals ; Cells, Cultured ; Glomerular Mesangium ; cytology ; Glucose ; pharmacology ; Mesangial Cells ; drug effects ; metabolism ; Metformin ; pharmacology ; NF-kappa B ; metabolism ; Rats

OBJECTIVE: To investigate the short-term effectiveness of ultrasound-guided closed reduction by Kirschner wire provocation technique in the treatment of Salter-Harris types Ⅰ and Ⅱ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents. METHODS: Between May 2019 and May 2022, 41 patients with Salter Harris types Ⅰ and Ⅱ distal tibial epiphyseal fractures were admitted, all of whom had periosteal entrapment on preoperative MRI, and 38 cases (92.7%) were confirmed to have periosteal entrapment by intraoperative ultrasound. There were 24 males and 14 females, the age ranged from 6.8 to 15.7 years, with an average of 10.7 years; and there were 20 cases of Salter Harris type Ⅰ and 18 cases of type Ⅱ. The time from injury to operation was 22-76 hours, with an average of 28.4 hours. The preoperative imaging examination showed excellent alignment in 4 cases, good in 20 cases, and poor in 14 cases. The ultrasound guided Kirschner wire provocation technique for closed reduction and percutaneous Kirschner wire internal fixation were performed. The operation time, intraoperative fluoroscopy frequency, fracture healing time, and complications were recorded. Anteroposterior and lateral X-ray films of the affected ankle joint were taken before operation, at 3 months after operation, and at last follow-up to observe the healing of the fracture, and anteroposterior X-ray films of the whole length of both lower limbs were taken to evaluate the alignment of the force lines of the affected limbs. The range of motion (ROM), visual analogue scale (VAS) score, and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were used to evaluate ankle function. The mechanical lateral distal tibia angle (mLDTA) and the anatomic anterior distal tibia angle (aADTA) were measured. RESULTS: The operation time ranged from 17 to 52 minutes, with an average of 22.6 minutes, and the intraoperative fluoroscopy frequency ranged from 3 to 11 times, with an average of 4.2 times. X-ray examination during operation and at 2 days after operation showed that anatomical reduction was achieved. All patients were followed up 10-24 months, with an average of 16.4 months. All fractures healed in 6.1-7.2 weeks, with an average of 6.3 weeks; no fracture displacement occurred, and the patients recovered to their pre-injury level of motion at 6 months after operation. Needle tail irritation occurred in 2 cases at 4 weeks after operation, and they recovered after symptomatic treatment. During the follow-up, there was no serious complication such as incision deep infection, bone nonunion, delayed union, and malunion. At last follow-up, the patients' alignment were all excellent, and the difference was significant when compared with preoperative one ( Z=-7.471, P<0.001). The VAS score, AOFAS ankle-hindfoot score, dorsiflexion-plantar flexion ROM, varus-valgus ROM, mLDTA, and aADTA significantly improved at 3 months after operation and last follow-up when compared with preoperative ones ( P<0.05). CONCLUSION Ultrasound-guided closed reduction by Kirschner wire provocation technique for treating Salter-Harris types Ⅰ and Ⅱ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents is minimally invasive and safe.
Male ; Female ; Child ; Humans ; Adolescent ; Tibia ; Bone Wires ; Treatment Outcome ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Ultrasonography, Interventional ; Retrospective Studies ; Tibial Fractures/surgery*

OBJECTIVE: To explore the effect of N,N-dimethylformamide( DMF)-induced inflammatory injury in H9c2 cardiomyocytes and its mechanism. METHODS: H9c2 cardiomyocytes were cultured in vitro and randomly divided into 4different groups: control group,50 mmol / L-group,100 mmol / L-group,200 mmol / L-group. These 4 groups of cells were treated with different DMF concentrations( 0,50,100,200 mmol / L) for 12 hours. The cells were also divided into 6groups and treated with 200 mmol / L DMF at different time points( 0,2,4,6,8,12 h) : control group,2 h-group,4 hgroup,6 h-group,8 h-group and 12 h-group. The level of lactate dehydrogenase( LDH) was detected by colorimetry. The levels of creatine kinase( CK) and isoenzyme of creatine kinase( CK-MB) were detected by ultraviolet spectrometry. The levels of tumor necrosis factor-α( TNF-α),interleukin( IL)-1β,IL-6,and IL-8 were detected by enzyme linked immunosorbent assay. The level of reactive oxygen species( ROS) was detected by fluorescence probe. The location of nuclear factor-kappa B( NF-κB) p65 protein was detected by immunofluorescence cytochemistry( IFC) staining. RESULTS: The levels of LDH,CK and CK-MB in the 50 mmol / L-group,100 mmol / L-group and 200 mmol / L-group were higher than that of the control group( P < 0. 05) and showed a significant dose-effect( P < 0. 05). The levels of LDH,CK and CK-MB in the 6 h-group,8 h-group and 12 h-group were higher than that of the control group( P < 0. 01) and showed a significant time-effect( P < 0. 01). The levels of TNF-α,IL-1β,IL-6 and IL-8 of the 200 mmol / L-group were higher than the control group( P < 0. 05). Compared with the control group,the levels of TNF-α of the 4 h-group,12 h-group were higher( P < 0. 05),the levels of IL-1β of the 2 h-group,4 h-group,6 h-group,8 h-group and 12 h-group were higher( P < 0. 05),the levels of IL-6 of the 2 h-group and 4 h-group were higher( P < 0. 05),the level of IL-8 of the 2 h-group was higher( P < 0. 05). In addition,the levels of TNF-α,IL-1β and IL-6 reached a peak at 4 h-group and the level of IL-8 reached a peak at 2 h-group. The ROS levels of the 2 h-group,4 h-group and 6 h-group were higher than the control group( P < 0. 01),and the level of ROS reached a peak at 2 h-group. Furthermore,IFC staining showed that the fluorescence intensity of NF-κB p65 protein in nucleus of the 2h-group and 4 h-group increased after treatment with DMF,comparing with the control group. CONCLUSION: DMF leads to inflammatory injury in H9c2 cardiomyocytes. ROS and NF-κB might be involved in the process.

Aim To explore the expression and possible effect of acid sensing ion channel-la( ASICla) in lung tissues of rats with acute lung injury ( ALI). Methods Thirty-two male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group, model group, amiloride group and Dex group. Blood gas analysis of arterial blood, observation of lung histo-pathology were performed and wet/dry ratio was calculated after weighing of lung tissues, then the expression of TNF-a in serum was detected by ELISA, and the expression of ASICla in lung tissues was also detected by qPCR and Western blot. Results Compared with control group, the lung tissue damage was obvious in model group, the wet/dry ratio of lung tissues obviously increased, and the expression level of TNF-a markedly increased (P < 0. 01 ). Lung tissue injury was significantly alleviated in amiloride group and Dex group, the wet/dry ratio of lung tissues obviously decreased , and the expression level of TNF-a significantly decreased (P < 0.01). Immunohistochemistry, qPCR and Western blot results showed that, compared with control group, the expression of ASICla significantly increased in model group (P <0.01), and markedly decreased in amiloride group (P <0.01). Conclusions The expression of ASIC 1 a increases in acute lung injury induced by lipopolysaccharide, which may be involved in the occurrence and development of ALI.

Aim: To study the therapeutic effects of recombinant human interleukin 1 receptor antagonist (rhIL-1ra) on type II collagen-induced arthritis (CIA) rats. Methods: SD rats were divided randomly into six groups including normal, model, rhIL-1ra (7.5,30,120 mg·kg-1) and anakinra(120 mg· kg-1) groups. Collagen II emulsion was used to induce CIA model in rats. The body weight was observed once a week. Paw swelling of CIA rats was measured with volume meter. C II induced delayed-type hypersensitivity (DTH) was measured. Meanwhile, the level of anti-C II IgG antibody in serum was assayed by ELISA. Results: The onset of paw swelling was on dlO after injection of emulsion. The level of serum anti-C II IgG antibody was increased significantly in CIA. Pathological changes in joints of CIA rats showed hyperplastic synovium of CIA, inflammatory cells infiltration, pannus, destruction of cartilage and bone. rhIL-1ra(7.5,30,120 mg·kg-1·d-1 x 7 d) and anakinra (120 mg·kg-1·d-1 x 7 d) subcutaneous injection (sc) inhibited inflammatory swelling. rhIL-1ra(30, 120 mg·kg-1·d-1 x 7 d) significantly suppressed the DTH reaction induced with C II in CIA rats. Moreover, rhIL-1ra reduced the level of anti-C II IgG antibody in serum. Pathological examination showed rhIL-1ra(120 mg·kg-1·d-1 x 7 d) significantly improved subchondral inflammation, synovium hyperplasia, pannus and cartilage damage. Conclusion: rhIL-1ra has therapeutic effects on CIA rats.

BACKGROUND: Currently, surgical methods for the treatment of degenerative scoliosis include simple decompression and decompression combined with internal fixation. However, there is still controversy over the choice of fixation and fusion segment in surgery, which requires more reliable evidence-based medical evidence for reference. OBJECTIVE: To evaluate the clinical efficacy and complication of short versus long segments of internal fixation for the treatment of degenerative scoliosis using meta-analysis. METHODS: CNKI, Wanfang Database, VIP, CBM, EMBase, PubMed, Web of Science, and Cochrane Library were searched to collect the randomized and non-randomized controlled studies which compared long fusion with short fusion in the treatment of degenerative scoliosis from inception to February 2019. Relevant conference papers and authoritative journals in the field were retrieved manually. The quality of the included studies was assessed by two evaluation members according to the Cochrane collaboration network standard or the Newcastle-Ottawa Scale. The included studies were analyzed by using RevMan 5.3 software. RESULTS AND CONCLUSION: (1) A total of 20 articles were included, involving a sample of 1 329 individuals. Long segment group consisted of 601 cases, and short segment group consisted of 728 cases. (2) The meta-analysis results showed that long-segment internal fixation surgery had better improvement of coronal Cobb angle (P=0.000 4), coronal balance (P=0.000 2), Oswestry disability index (P=0.003) and visual analogue scale score (P < 0.000 01). However, the incidence of implant failure (P=0.01) and dural tear (P=0.01) in short segment group was lower than that in long segment group. The short segment group had small trauma and shorter hospital stays after surgery (P < 0.000 1). (3) There was no statistical difference in other therapeutic indicators and complications between the two groups (P > 0.05). (4) These findings verify that long-segment internal fixation is superior to short-segment internal fixation in the correction of scoliosis, but the recovery is slow and the incidence of some complications after operation is high. It should be considered comprehensively when selecting specific surgical procedures.

Objective: To observe the effect of Astragalus polysaccharides (APS) on cardiac function and expression of Keap1/Nrf2-ARE signal pathway in adjuvant arthritis (AA) rats. Methods: Forty-eight rats were randomly divided into normal control (NC) group, model control (MC) group, leflunomide (LEF) group, and APS group. The AA model rats were induced with Freund's complete adjuvant, then administration began from day 19 after modeling for 30 d. The paw swelling and arthritic index (AI), the cardiac function indexes, the expression of Keap1, maf, Nrf2 mRNAs, and HO-1, r-GCS proteins in cardiac tissues were observed. Oxidation-related substances (SOD, MDA, ROS, and TAC) and cytokines (IL-10 and TNF-α) were also determined. Results: Compared with NC group, the paw swelling and AI were increased, and the body weight was decreased in MC group. HR, HI, LVSP, LVEDP, and levels of MDA, TAC, ROS, RNS, and TNF-α in MC group were increased, while dp/dtmax and levels of GSH, TRX, and IL-10 were decreased. Compared with MC group, LEF group showed higher HR and ± dp/dtmax, and lower LVEDP. In APS group, the HR, LVSP, and LVEDP were decreased and ±dp/dtmax was increased. TNF-α was decreased, TAC, ROS, MDA, and IL-10 were increased in both LEF and APS groups. APS and LEF groups also showed less MDA, TAC, ROS, and SOD, and the differences were statistically significant. Spearman correlation analysis showed that the cardiac function parameters were positively correlated with Keap1, anti-oxidant indicators, and anti-inflammation cytokines, and negatively correlated with Nrf2, oxidation indictors, pro-inflammation cytokines, and inflammation indictors. Conclusion: APS can adjust the expression of Keap1/Nrf2-ARE signal pathway in AA rats, and can also improve their cardiac function. The mechanism may be involved in increasing myocardial anti-oxidant capacity, reducing oxidative stress, and inhibiting inflammation.

OBJECTIVE: To provide reference for patients with type I incisions about rational use of antibiotics.METHODS: Between Oct.2007 and Mar.2008,a total of 1 024 medical records of patients with type I incisions from orthopaedics,common surgery,department of gynecology in 12 hospitals of Xining area were sampled for analysis of prophylactic use of antibiotics.RESULTS: 100.0% of the type I incision patients received prophylactic antibiotics;28.4% used antibiotics without indication;16.9% used antibiotics at 0.5～2 h before operation;33.4% used antibiotics at more than 2 h before operation;and 49.7% received antibiotics postoperatively rather than preoperatively.The irrational and nonstandard use of antibiotics manifested as improper in the choice of drug variety,nonstandard in drug combination,irrational in dosage and administration,prolonged use of antibiotics,lacking basis for the change of drug variety etc.CONCLUSION: The prophylactic use of antibiotics in patients with type I incisions from 12 hospitals of Xining area is far from perfect,therefore,it is urgent to strengthen the standard management on the use of antibiotics.

Objective To compare the pharmacokinetic effect of Platycodonis Radix in Painong Powder on naringin and paeoniflorin in rats, and study the compatibility effects of Platycodonis Radix. Methods A total of 12 healthy male SD rats were randomly divided into the Painong Powders full formula group and Painong Powder without Platycodonis Radix group; The solution of Painong Powders full formula and Painong Powder without Platycodi Radix was ig administrated to rats at dose of 16 g/kg. The blood was collected from theretinal vein plexus of rats at predetermined time and pre-prepared with liquiritin as internal standard (IS). UPLC-MS/MS was adopted to determine the contents of naringin and paeoniflorin. The chromatography was eluted with mobile phase consisted of 0.1% formic acid and methyl alcohol at a flow rate of 0.2 μL/min. ESI sources were adopted to scan in a negative ion scanning mode. Results After ig administration Painong Powder and Painong Powder without Platycodonis Radix, the main pharmacokinetic parameters of naringin were as follow: AUC0-t = (2 643.22 ± 277.75), (1 934.01 ± 371.98) μg∙h/L; Cmax = (597.57 ± 22.46), (477.13 ± 25.67) μg/L; CL = (821.96 ± 175.64), (542.21 ± 100.97) L/(h∙kg); Paeoniflorin showed AUC 0-t = (3 178.25 ± 235.97), (1 384.11 ± 320.11) μg∙h/L; Cmax = (816 ± 28.88), (402.67 ± 58.22) μg/L; CL = (1 102.27 ± 341.17), (482.59 ± 39.74) L/(h∙kg) (P<0.05). Conclusion Compared Painong Powders without Platycodonis Radix, the naringin and paeoniflorin in rat plasma showed similar pharmacokinetic changes after oral :201 administration Painong Powders full formula, such as the peak time was shortened, the rate of absorption, peak concentration, and the clearance were accelerated. This study proved scientific compatibility of Platycodonis Radix in Painong Powder and provided a reference for further study of the prescription compatibility regularity in Painong Powders.

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.
Cord Blood Stem Cell Transplantation ; Core Binding Factor Alpha 2 Subunit ; Graft vs Host Disease ; Humans ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; Oncogene Proteins, Fusion ; Peripheral Blood Stem Cell Transplantation ; RUNX1 Translocation Partner 1 Protein ; Transplantation Conditioning