The therapy to different type of breast cancer has resulted in chemoresistance which is induced by auto-phagy.Autophagy, to tumor’s generation, is a double edged sword, and it can result to chemoresistance and auto-phagic cell death through interaction with apoptosis in breast cancer chemotherapy.However, autophagy may be unrelated to chemoresistance.It will be a key research point to further explore the relationship and mechanism be-tween autophagy and chemoresistance.

Objective To investigate the role of glycogen synthase kinase-3β (GSK-3β) in the trafficking of NR1-containing N-methyl-D-aspartate receptor (NMDAR) and NR2B-containing NMDAR in the spinal cord in rats with incisional pain (IP) and remifentanil-induced hyperalgesia.Methods Twenty-four male Sprague-Dawley rats,aged 2-3 months,weighing 240-260 g,were randomly divided into 3 groups ( n =8 each):control group (group C),remifentanil group (group R) and GSK-3β inhibitor TDZD-8 group (group TDZD-8).A 1-cm longitudinal incision was made in the plantar surface of the left hindpaw in anesthetized rats.In group C,dimethyl sulfoxide (DMSO) 2 ml/kg was injected and then the normal saline (equal to the volume of remifentanil) was infused for 60 min via the caudal vein.In group R,DMSO 2 ml/kg was injected before IP was made and then remifentanil was infused at a rate of 1.2 μg· kg- 1 ·min- 1 for 60 min.In group TDZD-8,TDZD-8 2 ml/kg was injected before IP was made and then remifentanil was infused at a rate of 1.2 μg·kg-1 ·min-1 for 60 min.Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were measured 24 h before infusion of normal saline or remifentanil and at 2,6,24 and 48 h after intravenous injection.The rats were sacrificed after the last measurement of the pain threshold and L4-6 segment of the spinal cord was removed to determine the expression of NMDAR NR1 and NR2B subunits in cell membrane (s) and cytoplasm (i) in the spinal cord by Western blot analysis.The ratios of sNR1/iNR1 and sNR2B/iNR2B were calculated.Results Compared with group C,PWT was significantly decreased and PWL was significantly shortened,the expression of sNR1 and sNR2B was up-regulated,the expression of iNR1 and iNR2B was down-regulated,and the ratios of sNR1/iNR1 and sNR2B/iNR2B were significantly increased in groups R and TDZD-8 (P ＜ 0.05).Compared with group R,PWT was significantly increased and PWL was significantly prolonged,the expression of sNR1 and sNR2B was down-regulated,the expression of iNR1 and iNR2B was up-regulated,and the ratios of sNR1/iNR1 and sNR2B/iNR2B were significantly decreased in group TDZD-8 ( P ＜ 0.05).Conclusion GSK-3β is involved in the regulation of trafficking of NR1-containing NMDAR and NR2B-containing NMDAR from cytoplasm to cell membrane in the spinal cord in rats with IP and hyperalgesia induced by remifentanil.

OBJECTIVE To investigate the effect of arctigenin(ATG) on liver fibrosis in rats induced by carbon tetrachloride(CCl4)and to explore its underlying mechanism. METHODS Sprague-Dawley rats were randomly divided into six groups:vehicle,ATG 3.0 mg · kg-1 group,CCl4 model group,CCl4+ATG 1.0 and 3.0 mg·kg-1 groups,and CCl4+colchicine(COL)0.1 mg·kg-1(toxicity)group. Liver fibrosis was induced by subcutaneous injection of CCl4 in rats for 8 weeks. ATG and colchicine were administrated ig once a day starting from the fifth week after the CCl4 treatment for 4 weeks subsequent. At the end of the study,glutamic pyruvic transaminase (GPT),glutamic oxaloacetic transaminase(GOT),albumin(ALB),and total bilirubin (TBIL) as well as the contents of hydroxyproline (HYP) in liver tissues were measured. Histopathological changes were observed in the liver tissues using hematoxyline-eosin(HE)and Masson’s trichrome staining. The proliferation of hepatic stellate cells (HSC) and expression of cell cycle-related proteins were assayed by indirect immunofluores?cence staining and Western blotting,respectively. RESULTS Compared with CCl4 model group,ATG 1.0 and 3.0 mg · kg-1 improved the liver function by decreasing serum contents of GPT,GOT and TBIL (P<0.05),and increasing serum content of albumin(P<0.05). Histological results indicated that ATG 1.0 and 3.0 mg · kg-1 alleviated liver damage and reduced the formation of fibrous septa. Moreover, ATG 1.0 and 3.0 mg · kg-1 significantly decreased liver HYP when compared with CCl4 model group(P<0.05). In addition,CCl4-induced proliferation of activated HSC was inhibited by ATG 1.0 and 3.0 mg·kg-1, and this was accompanied by down-regulation of cyclin D1,cyclin-dependent kinase(CDK)2,CDK4, and proliferating cell nuclear antigen (PCNA)(P<0.05),and up-regulation of p27kip1 in activated HSC (P<0.05). CONCLUSION ATG can alleviate hepatic injury and fibrosis induced by CCl4,which is probably associated with suppression of the proliferation of activated HSC.

Objective To investigate the changes in total and surface N-methyl-D-aspartate receptor (NMDAR) NR1,NR2A and NR2B subunits in spinal cord in a rat model of incisional pain(IP)-remifentanil-induced hyperalgesia.Methods Thirty-two male SD rate in which caudal vein catheter were successfully placed were randomly divided into 4 groups ( n =8 each):control group(group C),remifentanil group(group R),IP group (group I) and IP + remifentanil group (group R + I).In groups R and C remifentanil 1.2 μg· kg-1 · min-1 or the same volume of normal saline was infused intravenously for60 main.In groups R + I and I,a 1 cm longitudinal incision was made in the plantar surface of left hindpaw and remifentanil 1.2 μg· kg-1 ·min-1 or the same volume of normal saline was infused intravenously for 60 min.Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were measured at 24 h before and 2,6,24,48 h after remifentanil or normal saline administration.The animals were sacrificed after last pain threshold measurement.The L4-6 segment of the spinal cord was isolated for determination of the expression of the total and surface NMDAR NR1,NR2A and NR2B subunits in spinal cord by Western blot.The ratio of surface NR2B/NR2A was calculated.Results Compared with group C,PWT was significantly decreased,PWL shortened,the expression of the total and surface NMDAR NR1,NR2A and NR2B subunits up-regulated and the ratio of surface NR2B/NR2A increased in groups 1,R and R + I( P ＜ 0.05).Compared with groups R and I,PWT was significantly decreased,PWL shortened,the expression of the total and surface NMDAR NR1,NR2A and NR2B subunits up-regulated and the ratio of surface NR2B/NR2A increased in group R + I( P ＜ 0.05).There was no significant difference in the total and surface NMDAR NR2A subunits among the four groups( P ＞ 0.05).Conclusion The up-regulation of total and surface NMDAR NR1 and NR2B subunits and the increased percentage of surface NR2B subunits in rats spinal cord may be involved in the development of incisional pain- remifentanil- induced hyperalgesia.

Objective:To explore the effect of delphinidin on breast cancer and the underlying mechanisms.Methods:Human epidermal growth factor receptor-2 (HER-2) positive breast cancer cells MDA-MB-453 were treated by delphinidin.Proliferation of MDA-MB-453 cells was detected by CCK-8 after 48 h.TdT-mediated dUTP nick end labeling (TUNEL) assay and Western blot were used to explore apoptotic status for MDA-MB-453 cells.Fluorescence dot assay,immunofluorescence,and Western blot were used to identify autophagy in breast cancer cells.Results:Delphinidin suppressed proliferation of MDA-MB-453 cells.Delphinidin increased the number of TUNEL positive cells.Delphinidin downregulated the expression of caspase-3 and caspase-9,while upregulated the expression of cleaved caspase-3 and cleaved caspase-9 in a dose-dependent manner.Delphinidin enhanced the number of GFP-LC3 punctate dots,LC3 immunofluorescence dots and the expression of LC3-Ⅱ and ATG5.Delphinidin inhibited the expression of proteins in mTOR signaling pathway,induding AKT,mTOR,eIF4E and p70s6k.Conclusion:Delphinidin induced apoptosis and autophagy by inhibition of AKT/mTOR pathway in HER positive breast cancer cells.

Objective To study the effect of gonadotropin releasing hormone agonist(GnRHa)against car-boplation-induced gonadotoxicity in rats. Methods Forty Wistar rats were divided into four groups which received carboplation, GnRHa + carboplation, GnRHa and normal saline respectively(n=10 for each group). Blood samples were collected from the abdominal aorta and the levels of blood follicle stimulation hormone (FSH) and estradiol (E<2>) were determined. Both ovaries and uterus of each rat were removed to measure the amount and the maturity of follicles. Body mass and morphological and pathological features of the rats were also observed. Results Compared with that in control group, the body mass of ovary and uterus decreased (P<0.05), and a significant reduction was observed in the number of ovarian follicles at each grade (P<0.05). The levels of E2 significantly lowered (P<0.05) and the level of FSH markedly ascended in group carboplation. Compared with that in group carboplation, the amount of primitive follicles significantly increased in group GnRHa + carboplation (P<0.05), and carboplation showed markedly protective effect on the ovarian and uterine morphological construction of rats. Conclusion Gn-Rha, appliying to preventing the rat reproduction damage in advance, has the certain protective function.

Objective To quantitatively evaluate the diagnostic value of blood oxygen leveldependent (BOLD) MRI in the diagnosis of different degrees of liver warm ischemia-reperfusion injury (WIRI) in rabbits and evaluate the intervention effect of liposomal prostaglandin E1 (Lipo-PGE1).Methods Seventy healthy adult New Zealand white rabbits were randomly divided into sham -operated group (A0),thermal ischemic groups (A1～A3) and intervention groups (A4～A6).All experimental rabbits were scanned by routine MR and BOLD MRI after 6-hour reperfusion.R2* images were calculated by two radiologists.The levels of alanine aminotransferase (ALT),asparate aminotransferase (AST) and lactate dehydrogenase (LDH) were examined.And liver pathological sectioning was performed.All data were processed by one-way,Spearman's correlation and receiver operating characteristic curve analyses.Results The intraclass correlation coefficient (ICC) was 0.805 of two measurements suggesting that the repeatability of the outcome was decent.R2* values among sham-operated,thermal ischemia and intervention groups were statistically significant (P＜0.05).R2 * values in sham-operated and ischemia groups were statistically significant (P＜0.05).As warm ischemia time elapsed,R2* value showed a rising trend.R2* values in sham-operated and intervention groups were statistically significant (P＜0.05).R2* values of sham-operated group at the same timepoint of thermal ischemia and intervention groups were statistically significant (P＜0.05).Under the same ischemic time,R2* values of intervention groups were smaller than those of thermal ischemia groups.With the prolongation of ischemia time,reduction of R2* values became more pronounced.However,it did not reach the level of A0 group.R2* values were significantly positively correlated with ALT,AST and LDH (r＞0.5,P＜0.05).ROC analysis indicated that R2* had an excellent diagnostic performance.Conclusions BOLD MRI may be applied for noninvasive assessment of liver ischemia-reperfusion injury in different degrees.Lipo-PGE1 alleviates ischemia -reperfusion injury and BOLD MRI can evaluate the relieving degree of Lipo-PGE1.

Objective To explore the effect of psychotherapy in patients with optic papilledema undergoing optic nerve sheath fenestration (ONSF).Methods Using convenience sampling method,a total of 64 patients with intracranial hypertension and optic papillary edema who were diagnosed by Ophthalmology Department of Xuanwu Hospital of Capital Medical University from 2013 to 2017 were selected as the subjects of study.All the subjects were randomly divided into two groups,with 32 patients in each group.Patients in the control group received routine ophthalmic nursing.The patients in the observation group were given six-step psychological intervention.Self-rating Anxiety Scale (SAS) were applied within 2 days after admission and before discharge to evaluate the patients.Results The score of SAS before discharge in the observation group was (46.28±4.48),which was lower than that in the control group (56.84±8.25),and the difference was statistically significant (t=6.363,P＜0.01).Conclusions Relevant psychotherapy can improve the anxiety of patients,so that patients can cooperate well with the treatment,which is worthy of clinical application.

Objective To investigate the risk factors and prognosis of acute kidney injury (AKI) after orthotopic liver transplantation (OLT).Methods The retrospective case-control study was conducted.The clinical data of 127 patients who underwent OLT in the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to December 2015 were collected.Of 127 patients,24 were complicated with postoperative AKI,including 17 in grade 1,5 in grade 2 and 2 in grade 3,and 103 were not complicated with AKI.AKI after OLT was treated according to the diagnostic criteria of AKI from 2012 guidelines of Kidney Disease:Improving Global Outcomes (KDIGO).Observation indicators:(1) risk factors analysis affecting AKI after OLT;(2) comparison of postoperative recovery in patients with different AKI grade;(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed up to July 2017.Measurement data with nornal distribution were represented as x±-s,and measurement data with skewed distribution were described as M (range).Univariate analysis was done using the t test and rank sum test.Comparisons of count data and univariate analysis were done using chi-square test or Fisher exact probability.Multivariate analysis was done using the logistic regression model.The survival rate and curve were respectively calculated and drawn by the KaplanMeier method,and Log-rank test was used for survival analysis.Results (1) Risk factors analysis affecting AKI after OLT:results of univariate analysis showed that age,combined hypertension,preoperative Child-Pugh score,preoperative model for end-stage liver disease score (MELD),preoperative hemoglobin,preoperative serum albumin,preoperative blood urea nitrogen,preoperative glomerular filtration rate,preoperative prothrombin time,operation time,inferior vena cava occlusion time,duration of anhepatic phase,volume of intraoperative blood loss,total volume of intraoperative blood transfusion,volumes of intraoperative plasma and red blood cells transfusion,duration of postoperative ICU stay,use time of postoperative vasoactive drugs,time of postoperative mechanical ventilation,cases with postoperative infection,body mass index of donor and donor liver cold-ischemia time were related factors affecting occurrence of AKI after OLT (t =4.154,x2 =8.482,t =5.129,3.694,1.294,9.223,5.418,Z=4.287,t=2.105,5.168,8.182,10.042,Z=1.074,0.664,6.274,3.712,1.289,t=1.056,x2 =10.617,t=2.447,3.371,1.476,P＜0.05).Results of multivariate analysis showed that age,preoperative MELD score,preoperative serum albumin,volume of intraoperative blood loss and donor liver cold-ischemia time were independent factors affecting occurrence of AKI after OLT [odds ratio (OR) =0.812,0.866,1.392,1.001,0.516,95％ confidence interval:0.717-0.919,0.751-0.997,1.104-1.755,1.000-1.001,0.282-0.944,P＜0.05].(2) Comparison of postoperative recovery in patients with different AKI grade:cases with complete recovery,partial recovery and chronic renal failure were respectively 14,3,0 in 17 patients with grade 1 of AKI and 3,2,0 in 5 patients with grade 2 of AKI and 0,1,1 in 2 patients with grade 3 of AKI,with a statistically significant difference (x2=14.140,P＜0.05).(3) Follow-up and survival situations:127 patients were followed up for 9-44 months,with a median of 23 months.The 1-year overall survival rate of 127 patients was 95.3％.During the follow-up,22 patients died,including 9 with multiple organ failure,8 with primary disease recurrence and 5 with respiratory complication.The median overall survival time after OLT was 36 months in 24 patients with AKI and 40 months in 103 patients without AKI,with no statistically significant difference (x2=3.033,P＞0.05).Conclusion Age,preoperative MELD score,preoperative serum albumin,volume of intraoperative blood loss and donor liver cold-ischemia time are independent factors affecting occurrence of AKI after OLT,and there is better recovery in patients with grade 1 of AKI.

Objective:To detective the cut-off values of amino acid levels in premature infants in Sichuan.Methods:Data of newborns screening for inherited metabolic diseases (IMD) by tandem mass spectrometry in Sichuan Province from January 2018 to December 2019 were retrospectively analyzed.They were divided into premature infant group ( n=2 264, 1 312 males and 952 females) and full-term infant group ( n=53 275, 28 269 males and 25 006 females). The cut-off values of amino acids in dry blood spots were expressed as percentage ( P0.5 - P99.5), and rank sum test was used for comparison between preterm and full-term infants. Results:(1) The distribution of 11 amino acids [alanine (ALA), arginine (ARG), citrulline (CIT), glycine(GLY), leucine (LEU), methionine (MET), ornithine (ORN), phenylalanine (PHE), proline (PRO), tyrosine (TYR) and valine (VAL)] in premature infants were abnormal.(2) The cut-off values of amino acids in premature infants were as follows: ALA: 135.20-552.33 μmol/L, ARG: 1.34-47.04 μmol/L, CIT: 5.66-32.02 μmol/L, GLY: 181.48-909.93 μmol/L, LEU : 71.10-283.29 μmol/L, MET: 4.21-34.51 μmol/L, ORN: 40.58-293.76 μmol/L, PHE: 23.60-106.30 μmol/L, PRO: 77.76-358.24 μmol/L, TYR: 27.52-352.91 μmol/L, VAL: 53.74-228.37 μmol/L.(3) The cut-off values of amino acid in full-term infants were as follows: ALA: 135.20-552.33 μmol/L, ARG: 1.30-42.73 μmol/L, CIT: 5.92-30.35 μmol/L, GLY: 208.17-980.09 μmol/L, LEU: 72.91-287.49 μmol/L, MET: 4.27-33.90 μmol/L, ORN: 48.40-305.59 μmol/L, PHE: 27.63-92.27 μmol/L, PRO: 97.38-372.75 μmol/L, TYR: 40.19-276.54 μmol/L, VAL: 65.75-237.92 μmol/L.(4) Except for PHE ( Z=-0.58, P>0.05), the other indicators were significantly different between 2 groups [ALA ( Z=-15.32, P<0.05), ARG ( Z=-5.62, P<0.05), CIT ( Z=-5.86, P<0.05), GLY ( Z=-14.52, P<0.05), LEU ( Z=-5.62, P<0.05), MET ( Z=-5.22, P<0.05), ORN ( Z=-13.01, P<0.05), PRO ( Z=-22.09, P<0.05), TRY ( Z=-2.09, P<0.05), VAL ( Z=-17.82, P<0.05)]. Conclusions:The establishment of the cut-off values of amino acids in premature infants in Sichuan provides a theoretical basis for laboratory diagnosis of IMD screening, which enhances the accuracy of diagnosis and avoids excessive medical treatment.