Akt is the downstream target protein of phosphatidylinositol 3-kinase(PI3K),and PI3K/Akt signaling pathway is involved in cell proliferation,differentiation,apoptosis and metabolism.The activities of Akt in the central nervous system is also regulated by the neurotransmitter dopamine(DA),therefore Akt mediates multiple drug addiction process.This article reviews the structural characteristics and activity regulation of Akt,as well as the related research in drug addiction of this signal molecule.

Objective To study the role of serum Hcy level change in predicting the effects of pemetrexed (PEM ) chemotherapy for treating the patients with advanced lung adenocarcinoma .Methods Fifty‐seven cases of lung adenocarcinoma treated by the PEM chemotherapy were retrospectively analyzed .The fasting venous blood was collected for detecting serum Hcy level before chemotherapy and at the end of 2‐week chemotherapy .The clinical characteristics ,Hcy level before and after chemotherapy and the relation between the Hcy level with clinical effect were statistically analyzed .Results In the therapeutic effects evaluated by the im‐aging examination during treatment process ,there were no case of complete remission (CR) ,19 cases of partial remission (PR) ,22 cases of stable diseases(SD) and 16 cases of progressed diseases(PD) ,the objective response rate(ORR) was 33 .3% and disease control rate (DCR) was 71 .9% .Different clinical factors had no significant influence on the efficacy of PEM chemotherapy (P>0 .05) .In comparing the influence of Hcy level and Hcy level change on the effect of PEM chemotherapy ,the results showed that serum Hcy level before treatment had no obvious influence on curative effect ,DCR in the patients with normal serum Hcy level after treatment was significant higher than that with abnormal Hcy level ,ORR and DCR in the patients with decreased Hcy level after chemotherapy were significantly higher than those with increased Hcy level (P<0 .05) .Conclusion Monitoring the serum Hcy lev‐el change during the PEM chemotherapeutic process in the patients with advanced lung adenocarcinoma may be used in the predic‐tion of the chemotherapeutic effect .

Objective To investigate the mechanism of AS2 O3 inducing the apoptosis of myelodysplastic syndrome(MDS) cell line SKM-1 .Methods SKM-1 cells were incubated with AS2 O3 ,and then the cellular morphology was observed ,flow cytometry was used to determine the apoptosis ,RT-PCR was used to detect the expressions of Bcl-2 ,Bax and caspase-3 mRNA .Results 0 .25、0 .50 μmol/L AS2 O3 could not markedly induce the apoptosis of SKM-1 cells (P>0 .05) .But 2 .00、8 .00、32 .00 μmol/L of AS2 O3 could obviously promote the apoptosis of SKM-1 cells .With the increase of the acting time and concentration of AS2 O3 ,the apoptosis rate increased ,too(P<0 .01) ,the expressions of anti-apoptotic gene Bcl-2 mRNA decreased (P<0 .01) ,the expressions of promoting apoptosis gene Bax and caspase-3 mRNA increased (P<0 .01 ,P<0 .05) .Conclusion 2 .00、8 .00、32 .00 μmol/L of AS2O3 may promote the apoptosis of SKM-1 cells through down-regulating the expression of Bcl-2 gene and up-regulating the ex-pressions of Bax and caspase-3 genes .

Objective To evaluate the two-stage repair in hypospadias cripples.Methods 35 patients with hypospadias cripples underwent two-stage repair.At the first stage,a full-thickness graft of skin or buccal mucosa was used for urethral plate reconstruction after the release of chordee.The second stage was performed 6 months after completion of the first stage.Tubularization of the replaced urethral plate was the preferred technique.Results There was no urethra stricture or “preplaced urethral plate ” atrophy.Fistula developed in 2 of 35 cases.Conclusion The twostaged technique was a useful strategy to deal with the myriad abnormalities encountered in crippled hypospadias.This technique could not only create a neourethra successfully,but also give the penis a near-normal shape and appearance.

OBJECTIVE To investigate the effect of injection of β2-adrenergic receptor agonist clenbuterol into the infralimbic cortex(IL) on drug-seeking behavior triggered by conditioned cues. METHODS Adult male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 d,followed by 2-h extinction training. Cue-induced heroin seeking was measured for 2 h. Clenbuterol was microinjected bilaterally into the IL(8 ng/side)of rats 15 min prior to reinstatement test. Meanwhile,locomotor activity was detected 15 min after clenbuterol or artifial cerebrospinal fluid(mod?el group) was microinjected bilaterally into IL. Western blotting was used to detect the expression of phosphorylated cyclic AMP response element-binding protein(p-CREB)in the prelimbic cortex(PL), IL,nucleus accumbens core (NACc) and shell (NACsh) of rats immediately after reinstatement test. RESULTS After heroin administration training for 14 consecutive days,these animals exhibited reliable heroin self-administration,indicated by the increase in active nose poke responses and infusions. The rats that had received infusion of clenbuterol into the IL had significantly lower active pokes (8 ± 3)than those in model group(45±10)in cue-induced reinstatement(P<0.01),but there was no significant differ?ence between clenbuterol group and vehicle group in the locomotor activity. The expression of p-CREB in either IL or NACsh was significantly decreased in clenbuterol group compared with model group(P<0.01,P<0.05),but significantly increased in NACc(P<0.01). CONCLUSION Microinjection of clenb?uterol into the IL can attenuate the cue-induced reinstatement of heroin-seeking behavior in rats. The underlying mechanism might be related to the regulation of p-CREB expression in the NACc and NACsh.

Objective To assess whether propofol call induce stable psychic dependence in the rats by self-administration experiment. Methods Twenty-four male SD rats 14 weeks old weighing 240一270 mg were studied. Anesthesia was performed with intraperitoneal injection of 3%sodium pentoharbitsl 40 ms/kg and atropine 03 mg/kg.A catheter wag inserted into the right external jugular vein. Penicillin(100 000 U)0.2 ml wag injected through the external jugular vein for anti-infection and heparin sodium(50U/ml)0.1 ml for anticoagulation. The self-administration experiment of 14 days was started after the 7 days of recovery. All the rats were randomly divided into 4 groups(n=6 each):contontrol group(C),propofol 0.56 mg/kg/l group(P1),propofol 1.00 mg/kg group(P2)and pmpofol 1.70 ms/kg group(P3).The experimental events were controlled by a computer with 50 times of the maximum injection per day.The times ofactive and inactive nose-poke response and times of drug iniection were recorded per day.Results Compared with group C and P1,the times of active nosepoke response and injections were significantly increased in group P2 and P3(P<0.01).The times of active nosepoke response and injections per day were significantly increased in group P3 than in group P2(P(0.01).There was no significant difference in the times of active nose-poke response and injections between group C and P1.There was no significant difference in inactive nose-poke resporme between the 4 groups.And the total daily doses of propofol injected in the last 3 days were significantly increased in a dose-dependent manner.Conclusion Propefol can induce the development of psychological dependence in rata and it is related to the dosage.

Nonspecific inflammatory response is the major cause for failure of islet grafts at the early phase of intraportal islet transplantation (IPIT). Bilirubin, a natural product of heme catabolism, has displayed anti-oxidative and anti-inflammatory activities. The present study has demonstrated that bilirubin protected islet grafts by inhibiting nonspecific inflammatory response in a syngeneic rat model of IPIT. The inflammation-induced cell injury was mimicked by exposing cultured rat insulinoma INS-1 cells to cytokines (IL-1beta, TNF-alpha and IFN-gamma) in in vitro assays. At appropriate lower concentrations, bilirubin significantly attenuated the reduced cell viability and enhanced cell apoptosis induced by cytokines, and protected the insulin secretory function of INS-1 cells. Diabetic inbred male Lewis rats induced by streptozotocin underwent IPIT at different islet equivalents (IEQs) (optimal dose of 1000, and suboptimal doses of 750 or 500), and bilirubin was administered to the recipients every 12 h, starting from one day before transplantation until 5 days after transplantation. Administration of bilirubin improved glucose control and enhanced glucose tolerance in diabetic recipients, and reduced the serum levels of inflammatory mediators including IL-1beta, TNF-alpha, soluble intercellular adhesion molecule 1, monocyte chemoattractant protein-1 and NO, and inhibited the infiltration of Kupffer cells into the islet grafts, and restored insulin-producing ability of transplanted islets.
Animals ; Apoptosis/drug effects/immunology ; Bilirubin/*administration & dosage/pharmacology ; Cell Line, Tumor ; Cytokines/immunology/metabolism ; Diabetes Mellitus, Experimental/*drug therapy/*immunology ; Inflammation ; Inflammation Mediators/immunology/metabolism ; Islets of Langerhans/drug effects/*immunology/injuries/pathology ; *Islets of Langerhans Transplantation ; Male ; Oxidative Stress/drug effects/immunology ; Rats ; Rats, Inbred Lew ; Transplantation, I

Objective:To compare ultrasound (US) guided versus computed tomography (CT) guided radiofrequency ablation (RFA) in treatment of early hepatocellular carcinoma (HCC).Methods:The data of 133 patients with early HCC treated by RFA in the Department of Hepatobiliary Surgery of Shandong Provincial Hospital from February 1, 2015, to January 31, 2017, was analyzed retrospectively. These patients were divided into two groups: the US-guided group and the CT-guided group. The clinical data was collected and the factors affecting prognosis were analyzed.Results:Compared with the CT-guided group, the operation time of the US-guided group was significantly shorter [(29.0±12.0)min vs. (55.0±19.0)min, P<0.05], but the number of ablation sessions per tumor was significantly less [(1.1±0.3) vs. (2.0±0.6), P<0.05]. There was no significant difference in the complete ablation rates, postoperative complication rates and postoperative length of hospital stay between the two groups ( P>0.05). The CT-guided group was superior to the US-guided group in the local tumor recurrence and progression-free survival rates ( P<0.05). On multivariate analysis, CT-guided RFA was an independent protective factor for local tumor recurrence ( HR=0.266, 95% CI: 0.073-0.967, P<0.05) and progression-free survival ( HR=0.415. 95% CI: 0.213-0.806, P<0.05), while AFP >20 ng/ml ( HR=4.821, 95% CI: 1.714-13.560, P<0.05) was an independent risk factor for progression-free survival. Conclusion:CT-guided percutaneous RFA was superior to US-guided RFA in local treatment of early HCC, probably related to more needle placements and longer ablation time under CT guidance.

Objective:To investigate the effect of preoperative use of diuretics on cardiac surgery-associated acute kidney injury(CSA-AKI)in elderly patients.Methods:In this single-center retrospective study, 1 638 patients aged ≥60 years and undergone cardiac surgery(including coronary artery bypass grafting, valve replacement and valvuloplasty)in the Department of Cardiovascular Surgery, Linyi People's Hospital between January 2015 and December 2022 were recruited.The last preoperative serum creatinine(SCr)level was taken as the baseline value, and AKI was diagnosed according to the Kidney Disease Improving Global Outcomes(KDIGO)criteria.Patients were divided into an AKI group and a non-AKI group according to whether AKI occurred after surgery.The clinical characteristics of the two groups were compared, and the effect of preoperative use of diuretics on CSA-AKI was evaluated by multivariate Logistic regression analysis.Results:Of 1638 patients enrolled in the study, 284 patients(17.3%)developed CSA-AKI.Compared with the non-AKI group, there were higher proportions of patients in the AKI group receiving furosemide(62.7% or 178/284 vs.46.2% or 626/1 354, χ2=25.397, P<0.001), spironolactone(70.1% or 199/284 vs.49.9% or 676/1 354, χ2=38.284, P<0.001), and hydrochlorothiazide(8.1% or 23/284 vs.3.5% or 47/1354, χ2=12.288, P<0.001). The number of diuretics in the AKI group was higher than in the non-AKI group[2(0, 2) vs.1(0, 2), Z=-6.381, P<0.001], and the proportion of patients using ≥2 diuretics was higher in the AKI group than in the non-AKI group(70.1% or 199/284 vs.49.0% or 664/1354, χ2=41.652, P<0.001). Multivariate Logistic regression analysis showed that, after adjusting for hypertension, diabetes mellitus, hypoalbuminemia, NYHA functional class Ⅲ/Ⅳ, cardiopulmonary bypass during surgery, operative duration≥6 h, postoperative blood transfusion>600 ml, postoperative use of >3 vasoactive drugs and other variables, preoperative use of ≥2 diuretics remained an independent risk factor for CSA-AKI in elderly patients( OR=1.580, 95% CI: 1.042-2.396, P=0.031). Conclusions:AKI is a common complication after cardiac surgery in elderly patients.Preoperative use of ≥2 diuretics used may be an independent risk factor for CSA-AKI.

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.