Drug Resistance ; Glucocorticoids ; therapeutic use ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Membrane Proteins ; genetics ; Mutation ; Nephrotic Syndrome ; drug therapy ; genetics

Objective To evaluate the role of AMP-activated protein kinase (AMPK)-dependent autophagic signaling pathway in ketamine-induced reduction of diabetic neuropathic pain (DNP) in rats.Methods Sixty male Wistar rats,aged 3 months,weighing 200-250 g,were equally randomized into 5 groups using a random number table:control group (C group),normal saline group (NS group),ketamine group (K group),ketamine + Compound C group (KC group),and ketamine + 3-methyladenine (3-MA) group (KM group).DNP model was established by intraperitoneal injection of streptozocin (STZ)65 mg/kg in anesthetized rats.Four weeks later,the equal volume of normal saline,ketamine 10 mg/kg,ketamine 10 mg/kg + Compound C1 mg/kg,and ketamine + 3-MA 2 μl were injected intraperitoneally once a day for 7 consecutive days in NS,K,KC and KM groups,respectively.The mechanical paw withdrawal threshold (MWT) was measured on 8th day.The rats were then sacrificed,and the lunbar segment (L1-5) of the spinal cord was removed for determination of the expression of AMPKαt,Beclin-1,microtubule-associated protein 1 light chain (LC) 3B (by Western blot) and dendritic spine density in the dorsal root ganglia.Results Compared with group C,the MWT,expression of AMPKα,Beclin-1,and LC3B,and dendritic spine density were significantly decreased in group NS (P＜0.05).Compared with group NS,the MWT,expression of AMPKαt,Beclin-1,and LC3B,and dendritic spine density were significantly increased in group K (P＜0.05).Compared with group K,the MWT,expression of AMPKα,Beclin-1,and LC3B,and dendritic spine density were significantly decreased in KC and KM groups (P＜0.05).Conclusion Activation of AMPK-dependent autophagic pathway is involved in ketamine-induced reduction of DNP in rats.

Objective To detect anti-clinically amyopathic dermatomyositis (CADM)-140 antibody in patients with dermatomyositis (DM) or CADM,and to estimate its clinical correlation.Methods Serum samples were collected from 22 patients with DM,16 patients with CADM,46 patients with other connective tissue diseases complicated by interstitial lung disease(including 8 cases of polymyositis,15 cases of systemic lupus erythematosus,5 cases of systemic sclerosis,6 cases of Sj(o)gren syndrome,6 cases of mixed connective tissue disease,6 cases of idiopathic pulmonary fibrosis),and 5 normal human controls.Enzyme-linked immunosorbent assay (ELISA) was performed with the recombinant melanoma differentiation-associated gene 5(rMDA)as a substrate to measure the anti-CADM-140 antibody in these serum samples.Clinical manifestations were compared between patients with anti-CADM-140 antibody and those without.Results The anti-CADM-140antibody was found in 43.8% (7/16) of patients with CADM and 9.1%(2/22) of patients with DM(P<0.05),but absent in the patients with other connective tissue diseases and in the normal human controls.A significant incroase was observed in anti-CADM-140 antibody-positive patients with DM/CADM in the incidence of cutaneous ulceration and necrosis,interstitial lung disease and rapidly progressive interstitial lung disease (8/9 vs.6.9%,P<0.01;9/9 vs.48.3%,P<0.01;5/9 vs.0,P<0.05),serum lactate dehydrogenase level(328.3±104.2 vs 241.1±100.3 IU/L P<0.05),erythrocyte sedimentation rate(40.8±23.1 vs.22.5±16.8 mm/1 h,P<0.05),high resolution computed tomography score(122.9±54.8 vs.70.0±59.8,P<0.05)compared with anti-CADM-140 antibody-negative patients with DM/CADM.The ereatine kinase level was significantly lower(156.3±260.8 vs.1806.2±3737.1 IU/L P<0.05)in anti-CADM-140 antibody-positive patients with DM/CADM than in anti-CADM-140 antibody-negative patients with DM/CADM,while no significant difference was noted in the positivity rate of antinuclear antibodies or incidence of malignancies between the antibody-positive and-negative patients with DM/CADM.Conclusions Anti-CADM.140 antibody not only is useful for the diagnosis of interstitial lung disease in patients with DM/CADM,but also may serve as a serum marker for rapidly progressive interstitial lung disease.Monitoring of serum anti-CADM-140 antibody might help to predict the progression of interstitial lung disease in patients with DM/CADM.

Breast Neoplasms ; genetics ; pathology ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 9 ; Female ; Genome, Human ; Humans ; Nucleic Acid Hybridization ; methods ; Phyllodes Tumor ; genetics ; pathology

Aim To study absorption characteristics of SM-1 , a novel anti-tumor agent , to provide a research basis for the druggability evaluation of SM-1 and formu-lation design. Methods Caco-2 cell monolayer model and in situ single-pass intestinal perfusion rat model were used to study the absorption characteristics of SM-1 , and the absorption of SM-1 in vivo was evaluated through absolute bioavailability study in rats. Results The results of cell monolayer model showed that cu-mulative absorption and efflux of SM-1 increased line-arly with concentration ( 10 ~40 mg · L-1 ) . There were no significant differences in Papp with different concentrations ( P>0. 05 ) . SM-1 was absorbed mainly through passive diffusion. The intestinal perfusion re-sults showed that Ka and Pef of SM-1 had no significant differences ( P > 0. 05 ) , when the concentrations ranged from 25 to 100 mg · L-1 . SM-1 entered the systemic circulation mainly via on passive diffusion, indicating it is a compound with high permeability. The absorption of SM-1 in duodenum was superior to other intestinal segments ( P <0. 05 ) , there were no significant differences in the jejunum, ileum and colon ( P >0. 05 ) . The absolute bioavailability of SM-1 in rats was 29. 3%. Conclusion The membrane perme-ability of SM-1 is high and it can be absorbed by intes-tine well. The absorption mechanism of SM-1 is pas-sive diffusion, and it possibly escapes from the efflux transporter protein. The absolute bioavailability of SM-1 in rats is low.

Objective To compare different incidence between lateral position and horizontal position in the Burr holes irrigation drainage(BHID).The BHID is wildly known as the most frequently used neurosurgical treatment of chronic subdural hematoma(CSDH).Methods A total of 80 cases were selected which were undergone BHID during January 2010 and December 2015,and the incidence of intracranial pneumatocele was compared after operation.All of cases came from the Second People′s Hospital of Tai Zhou City.Results There were 5 cases(out of 50,10%)having moderate intracranial pneumocephalus but no numerous intracranial pneumocephalus in lateral position,while 26 cases(out of 30 cases,87%)in horizontal position emerging moderate amount or more intracranial pneumatocele.And there were 8 cases'numerous pneumatocele in the horizontal postion group.There was no tension pneumothorax emerging in both groups.Both groups had statistical difference (χ2 =46.43,P <0.01.Conclusion BHID in lateral postion is a simple and effective method for CSDH,and it is conducive to reduce postoperative intracranial pneumatosis.That is worthy of application and promotion.

Objective To study the radiosensitizing effect of nano-gold nano-silver particles in hepatocellular carcinoma cells (HepG2) in vitro and the possible mechanisms.Methods MTT assay and clonogenic assay were performed to determine the killing effect of nano-gold and nano-silver particles in HepG2 cells.Flow-cytometry was used to measure cell apoptosis and cell cycle distribution.Western blotting was used to measure the expression of Caspase-3,Bax and Bcl-2.ELIASA was used to determine the content of catalase (CAT),superoxide dismutase (SOD),and total glutathione (GSH).Results Nano-gold and nano-silver particles inhibited the proliferation of HepG2 cells with IC50 of 6.51 μg/ml and 2.47 μg/ml,respectively.Nano-gold and nano-silver particles significantly enhanced the radiosensitivity of HepG2 cells.Obtained by Dq,the SER of 1/5 IC50 nano-gold and nano-silver particles were 1.37 and 1.48,and 1/10IC50 with 1.11 and 1.09.Nano-gold and nano-silver particles increased the expression of Caspase-3 and Bax and reduced the exprcssion of Bcl-2.CAT,SOD and total GSH were significantly reduced.Conclusions Nano-gold and nano-silver particles can enhance the radiation sensitivity of HepG2 cells.Specific sensitizing mechanism may be the activation of the mitochondrial apoptosis pathway and the induction of reactive oxygen species in apoptotic pathways,which ultimately induces apoptosis.

Objective To develop an efficient method for the determination of activity of human lymphocyte kynureninase by high performance liquid chromatography. Methods Protein containing kynureninase was extracted from lymphocytes.The reaction was made with 3-hydroxyanthranilic acid as substrate and pyridoxal-5'-phosphate as coenzyme.The product was determined by high performance liquid chromatography and fluorescence detection.(Results)Standard curve of 3-hydroxyanthranilic acid was highly linear over the range from 2 to 400 nmol/L.The intra-day coefficient of variation(CV) was less than 3.0% and the inter-day CV was less than 3.2%. Conclusion(The developed) assay is efficient and can be used to determine the activity of kynureninase from kinds of tissues.

Objective To evaluate the significance of CT assessment for extraarticular anatomy in treatment of displaced intraarticular calcaneal fractures.Methods(1)Measurement of normal calcaneum 40 pieces of adult calcaneum specimen were measured,items of measurement included height of culmination of posterior facet and tuberosity,width of posterior edge of sustentaculum and tuberosity.(2)CT measurement of calcaneum.Transverse(axial)and coronal CT scanning were obtained from 20 feet with displaced intraarticular calcaneal and 20 normal feet as control.Following items were measured in CT scanning:the height of culmination of posterior facet and tuberosity,the coronal talocalcaneal angle,in coronal scanning,the width of posterior edge of sustentaculum and tuberosity,the axial calcaneocuboid angle,in axial scanning.Results(1)Measurement of height of calcaneum height of culmination of posterior facet and tuberosity of calcaneal specimen were(43.07?2.85)mm and(44.69?3.67)mm respectively,and these two items from CT scanning of normal feet were(42.84?1.66)mm,(43.40? 3.01)nun,and from CT scanning of feet with calcaneal fractures were(34.76?3.24)mm,(40.41? 3.69)mm.There was a statistically significant different between these two items for normal calcaneal specimen and for CT scanning of feet with ealcaneal fractures(P

Objective To explore the value of susceptibility-weighted imaging (SWI) for the assessment of chronic renal injury. Methods Thirty-nine patients with clinical diagnosis of chronic renal injury (RI group) who underwent routine renal MRI and SWI examination were retrospectively analyzed. They were divided into mild injured group (15 cases) and moderate to severe injured group (24 cases) by estimated glomerular filtration rate (eGFR). At the same time, 17 volunteers without chronic renal injury who had normal serum creatinine (Scr) and blood urea nitrogen were recruited as control group. All subjects underwent routine renal MRI and SWI examination. The ratios of cortex to medulla were measured and calculated in both kidneys' magnitude image and susceptibility weighted image, which were indicated as C/MMAG and C/MSWI. Independent sample t test was used to compare the differences of C/MMAG and C/MSWI between control group and RI group, and paired sample t test was used to compare the differences betweenC/MMAG and C/MSWI in each group. One-way ANOVA was used to compare the difference of C/MMAG and C/MSWI between the control group and the different RI groups. ROC was employed to assess the diagnostic efficacy of C/MMAG and C/MSWI in renal injury. Pearson linear correlation analysis was used to evaluate the correlation between C/MMAG, C/MSWI and eGFR, Scr in patients with renal injury. Results The C/MMAG and C/MSWI in the RI group were 1.101±0.039 and 1.071±0.046, respectively. C/MSWI was obviously lower than C/MMAG, and the difference was statistically significant (t=5.056, P<0.01). There was no significant difference between C/MMAG and C/MSWI in the control group (P>0.05). The C/MMAG and C/MSWI in the RI group were obviously lower than those in the control group, and the difference was statistically significant (t=4.564, 6.122;P<0.01).The C/MMAG and C/MSWI in the mild injured group and the moderate to severe injured group were significantly lower than those in the control group, the difference was statistically significant (P<0.05). While the differences of those between mild injured group and moderate to severe injured group showed no statistical significance (P>0.05). The area under ROC of C/MMAG and C/MSWI in diagnosis of renal injury were 0.853 and 0.952, respectively. C/MMAG was positively correlated with eGFR (r=0.460,P<0.01). Conclusions Susceptibility-weighted imaging can be used to assess chronic renal injury. Although it cannot reflect the degree of renal function damage, it has some value in the early diagnosis of mild renal injury.