Objective To study the relationship between the expression of inducible nitric oxide synthase(iNOS)and neural cell apoptosis after chronic cauda equina compression. Methods Totally 30 male adult SD rats were randomly divided into 2 groups as the control group and the experi?mental group. The control group received sham operation with single laminectomy of L5 lumina. In the experimental group,the silicon sheet was in?serted into the spinal canal of L4 to cause single level compression of cauda equina. The L4 level of spinal cords were harvested at 2 weeks,4 weeks,8 weeks,and 12 weeks after operation in the experimental group,and at 4 weeks in the control group respectively,and then immunohistochemistry and image analysis were performed to observe the expression of iNOS in spinal cord and the TUNEL method was applied to observe cell apoptosis. The morphology of cells was observed by transmission electron microscope. Results There was few amount of iNOS expressed in the control group. The expression of iNOS was slight at 4 weeks in the experimental group and was higher at 8 weeks and 12 weeks compared with the control group. Small amount of neural cell apoptosis was evidenced in the control group,while neuron apoptosis appeared remarkably in the experimental group since 4 weeks and increased with the extension of time. Transmission electron microscopy found apoptosis changes in neurons in the experimental group. Conclusion The expression of iNOS increases in corresponding spinal cords after chronic compression of cuada equine and neural cell apoptosis oc?curs,indicating that iNOS is positively correlated with neural cell apoptosis.

[ ABSTRACT] AIM:To explore whether IL-1βinhibits the oligodendrocyte precursor cell ( OPCs) differentiation and affects axonal myelination.METHODS:One-day-old SD rats were randomly divided into control group and LPS group ( 48 rats in each group) .The rats in LPS group were intraperitoneally injected with 1 mg/kg LPS.The rats in control group were injected with an equal volume of PBS.The rats in each group were further divided into 3 h, 24 h, 3 d, 7 d, 14 d and 28 d subgroups after injection.The expression of IL-1βand IL-1R1 in the rat corpus callosum at 3 h, 24 h, 3 d, 7 d was determined by double immunofluorescence and Western blotting.The myelin basic protein( MBP) expression in the rat cor-pus callosum at 14 d, 28 d after injection was also measured.In vitro, primary OPCs culture was performed and divided in-to control group, 30 μg/L IL-1βgroup, 30 μg/L IL-1β+IL-1Ra group and 30 μg/L IL-1Ra group.The expression of MBP in the OPCs induced differentiation for 3 d was observed by double immunofluorescence and Western blotting.RE-SULTS:The expression of IL-1βand IL-1R1 in the rat corpus callosum at 3 h, 24 h, 3 d, 7 d after LPS injection was ob-viously increased and the expression of MBP in the rat corpus callosum at 14 d, 28 d in LPS group was obviously decreased compared with control group in vivo.The level of MBP was significantly decreased after IL-1βtreatment for 3 d in vitro. However, IL-1Ra (IL-1R inhibitor) reversed the down-regulation of MBP expression.IL-1βinhibited the expression of p-ERK, ERK over-expression reversed the down-regulation of MBP expression compared with IL-1βgroup.CONCLUSION:IL-1βinhibits the differentiation of OPCs, which may be involved in ERK pathways, thus leading to axonal hypomyelination in the corpus callosum of septic neonatal rats.

AIM: To investigate alteration of inward re ctifier potassium current (I K1) in atrial myocytes and mRNA expression of gene Kir2.1 encoding I K1 in atrial myocardial tissue in patients with chronic atrial fibrillation (AF) compared to that with sinus rhythm (SR).METHODS: Single myocytes were isolated by enzymatic dissociation with the chunk method an d the ionic current was recorded using whole cell patch clamp technique. The sem i-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of Kir2.1 in atrial myocardial tissue, and the g ene GAPDH was used as an internal control.RESULTS: (1) The I K1 density was increased in AF group at hyperpolarizing pot entials, at -120 mV the current densities was (-5.71?0.65) pA/pF in AF group (n=28 cells from 7 patients) and (-4.26?1.22) pA/pF in SR group (n=35 cells from 9 patients) (P0.05).CONCLUSIONS: The increase in I K1 at hyperpolarizing potentials may be related to th e atrial electrophysiological remodeling in chronic human AF. The increased I K1 density in atrial myocytes in AF group without alteration of Kir2.1 mRNA expression in atrial tissue suggests that I K1 may be mediated at post-transcriptional levels.

Objective: To evaluate the short-term effect of arthroscopic Endobutton combined with Orthocord suture fixation for tibia eminence fracture of anterior cruciate ligament in adults. Methods: The data of 9 adult patients with tibia eminence fracture of anterior cruciate ligament treated with Endobutton combined with Orthocord suture fixation from April 2017 to October 2018 were retrospectively analyzed. The range of motion of knee joint and the stability of knee joint were recorded 3 and 6 months after operation. Results: All patients were followed up for 3 and 6 months after operation. CT examination showed fracture reduction and healing 2 months after operation, and magnetic resonance image examination showed good anterior cruciate ligament tension 3 months after operation. The range of motion of knee joint was 0°-130° after 3 and 6 months, and Lanchman test was negative. The Lysholm score was (45.2 ± 6.7) scores, and IKDC score was (55.1 ± 7.3) scores before operation. The Lysholm score was (89.1 ± 7.2) scores, IKDC score was(87.4 ± 6.1) scores, Lysholm score was (95.4 ± 6.5) scores and IKDC score was (93.2 ± 7.8) scores at 6 months after operation. Conclusions Endobutton combined with Orthocord suture fixation under arthroscopy has a good short-term effect in the treatment tibia eminence fracture of anterior cruciate ligament in adults.

The present research was to study the biocompatibility of a composite of hydroxyapatite (HA), carbon fiber (CF) and polyetheretherket-one (PEEK) by co-culturing with the osteoblasts in vitro. Cell relative growth (RGR) was used as a quantitative assessment for cytotoxicity of the biomaterials by CCK-8. The proliferation index of the co-cultured cells and ALP activity was measured to study the effect of PEEK-HA-CF composites. Morphological properties of the osteoblast cells in vitro were observed by scanning electro-microscopy (SEM). The PEEK-HA-CF materials have no cytotoxicity to osteoblasts. The proliferation index of PEEK-HA-CF was higher than that of Ti alloy group, but these was no significant difference compared to that of control group. The ALP activity was the highest on PEEK-HA-CF composites surface after 7 days. The osteoblast cells co-cultured with the PEEK-HA-CF composite were adhered well to the biomaterial as observed under the SEM. The results suggested that the PEEK-HA-CF composites had good biocompatibility in vitro and might be a novel orthopedic implanted material.
Alkaline Phosphatase ; metabolism ; Animals ; Biocompatible Materials ; Carbon ; chemistry ; Cell Proliferation ; drug effects ; Cells, Cultured ; Durapatite ; chemistry ; Ketones ; chemistry ; Orthopedics ; Osteoblasts ; chemistry ; Polyethylene Glycols ; chemistry ; Prostheses and Implants ; Rats

Objective To investigate the changes in the expression levels of miR-21 and its regulatory proteins in bone tissues of osteoporotic mouse model, and its correlation with bone mineral density. Methods Thirty ovariectomized (ovx) female mice were randomly divided into six groups according to different observation time (0 week, 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks, respectively). Smad7 expression level in the tissues of the distal femur of these mice was immunohistochemically analyzed. Real time PCR was performed at different time points for detecting changes in the mRNA levels of miR-21 and Smad7 target genes in the bone tissue. Dual-energy X-ray absorptiometry (DXA) was used to measure the distal femoral bone density in mice of each group. Results Immunohistochemical study revealed that the expression of Smad7 in the bone tissue of osteoporostic mouse gradually increased over time. Real time PCR analysis showed that the expression of mi R-21 gradually decreased, whereas the expression of Smad7 gradually increased. Over time, the bone density of mice gradually decreased, indicating that miR-21 was positively correlated with bone density, whereas Smad7 was negatively correlated with bone density. Conclusion Bone density of the osteoporotic mice gradually decreases. The expression of miR-21 is positively correlated with bone density, while that of Smad7 is negatively correlated with bone density.

Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.

BACKGROUNDLittle is known about the value of (31)P-magnetic resonance spectroscopy ((31)P-MRS) in in vivo assessment of exhaustive exercise-induced injury in skeletal muscle. We aimed to evaluate the value of a (31)P-MRS study using the quadriceps femoris after a single bout of acute exhaustive swimming in rats, and the correlation between (31)P-MRS and histological changes.

METHODSSixty male Sprague-Dawley rats were randomly assigned to control, half-exhaustive, and exhaustive exercise groups. (31)P-MRS of the quadriceps femoris of the right lower limb was performed immediately after swimming exercise to detect Pi, PCr, and β-ATP. The Pi/PCr, Pi/β-ATP, PCr/β-ATP, and PCr/(PCr+Pi) were calculated and pH measured. Areas under the receiver operating characteristic curve (AUCs) were calculated to evaluate the diagnostic potential of (31)P-MRS in identifying and distinguishing the three groups. HE staining, electron microscopy and desmin immunostaining after imaging of the muscle were used as a reference standard. The correlation between (31)P-MRS and the mean absorbance (A value) of desmin staining were analyzed with the Pearson correlation test.

RESULTSPi, PCr, Pi/PCr, and PCr/(PCr+Pi) showed statistically significant intergroup differences (P < 0.05). AUCs of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were 0.905, 0.848, 0.930, and 0.930 for the control and half-exhaustive groups, while sensitivity and specificity were 90%/85%, 95%/55%, 95%/80%, and 90%/85%, respectively. The AUCs of Pi, PCr, Pi/PCr and PCr/(PCr+Pi) were 0.995, 0.980, 1.000, and 1.000 for the control and exhaustive groups, while sensitivity and specificity were 95%/90%, 100%/90%, 100%/95%, and 100%/95%, respectively. The AUCs of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were 0.735, 0.865, 0.903, and 0.903 for the half-exhaustive and exhaustive groups, while sensitivity and specificity were 80%/60%, 90%/75%, 95%/65%, and 95%/70%, respectively. In the half-exhaustive group, some muscle fibers exhibited edema in HE staining, and the unclear Z-discs and the mitochondria with vacuolar degeneration under electron microscopy. Compared with the half-exhaustive group, muscle fiber edema was increased in the exhaustive group, and the Z-discs were broken and the mitochondria exhibited marked vacuolar degeneration under electron microscopy. There were significant difference in A values of desmin staining in the right vastus lateralis among the control, half-exhaustive, and exhaustive groups with 0.58 ± 0.06, 0.30 ± 0.04, and 0.21 ± 0.02, respectively (P < 0.05). Histological examination also showed injury-induced changes in the vastus lateralis among the different intensities groups. Statistically a moderate correlation between (31)P-MRS and desmin was observed, the correlation coefficients of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were -0.706, 0.709, -0.726, and 0.791, respectively (P < 0.01).

CONCLUSIONS(31)P-MRS can effectively reflect the changes in energy metabolism in the skeletal muscle after a single bout of acute exhaustive swimming in rats. Based on the significant correlation between (31)P-MRS parameters and histological changes, the changes of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) can indirectly reflect the degree of exercise-induced injury.

Animals ; Energy Metabolism ; physiology ; Magnetic Resonance Spectroscopy ; methods ; Male ; Physical Conditioning, Animal ; physiology ; Quadriceps Muscle ; metabolism ; Rats ; Rats, Sprague-Dawley

Opioid analgesics are currently known as the best analgesics. However， toxicity and side effects such as constipation， tolerance and addiction severely limit their clinical application. With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology， researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics， which are different from the traditional morphine skeleton structure modifications. This article focuses on three new research strategies of G-protein biased activation，“ one drug-multiple targets” and peripheral activation. The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced， and the latest research progress of representative drugs is briefly reviewed. Among them， the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists， Cebranopadol is a typical “one drug-multiple targets” analgesic， and NFEPP is a representative drug of peripheral opioid receptor agonists. The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.