Background: The function of CD69 expressed on T cells in chronic hepatitis B (CHB) remains unclear. We aimed to elucidate the roles of CD69 on T cells in the disease process and in antiviral therapy for CHB. Methods: We enrolled 335 treatment-naive patients with CHB and 93 patients with CHB on antiviral therapy. CD69, antiviral cytokine production by T cells, T-helper (Th) cells, and inhibitory molecules of T cells were measured using flow cytometry, and clinical-virological characteristics were examined dynamically during antiviral therapy. Results: CD69 expression on CD3+, CD4+, and CD8+ T cells was the lowest in the immune-active phase and was negatively correlated with liver transaminase activity, fibrosis features, inflammatory cytokine production by T cells, and Th-cell frequencies but positively with inhibitory molecules on T cells. CD69 expression on CD3+, CD4+, and CD8+ T cells decreased after 48 weeks of antiviral therapy, and patients with hepatitis B e antigen (HBeAg) seroconversion in week 48 showed lower CD69 expression on T cells at baseline and week 48. The area under the ROC curve of CD69 expression on T cells at baseline for predicting HBeAg seroconversion in week 48 was 0.870, the sensitivity was 0.909, and the specificity was 0.714 (P = 0.002). Conclusions CD69 negatively regulates T-cell immunity during CHB, and its expression decreases with antiviral therapy. CD69 expression predicts HBeAg seroconversion in week 48. CD69 may play an important negative role in regulating T cells and affect the efficacy of antiviral therapy.

Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1α (HIF-1α), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
Animals ; Mice ; Ferroptosis ; Network Pharmacology ; Reactive Oxygen Species ; Vascular Endothelial Growth Factor A ; Influenza A virus ; Iron ; Hypoxia

AIM:To investigate the effects of ethane 1,2-dimethanesulfonate (EDS) preconditioning on renal ischemia/reperfusion (I/R) injury in male Sprague-Dawley (SD) rats.METHODS: Male SD rats (n=48) were ran-domly assigned to 6 groups:blank, sham, I/R, EDS+I/R, EDS+testosterone (TST) +I/R, and castration (Cast)+I/R.The renal pedicles were bilaterally occluded with a microvascular clamp for 45 min to establish renal I/R-induced in-jury model.Bilateral orchiectomy was conducted 2 weeks before surgery .EDS (75 mg/kg) was intraperitoneally injected 5 d before operation .Blood samples were collected 24 h after reperfusion from the vena orbitalis posterior plexus .Luteinizing hormone (LH), TST, serum creatinine (SCr), blood urea nitrogen (BUN), and kidney injury molecule-1 (KIM-1) were detected.The renal tissues were harvested to measure the level of TNF-αand the expression of Fas mRNA and caspase-3 protein.RESULTS:Serum TST levels in EDS +I/R group and Cast +I/R group were below the minimum detectable threshold.Compared with other groups , the rats in EDS+I/R group and Cast +I/R group had higher levels of SCr , BUN and KIM-1 (P<0.05).SCr and BUN levels showed no significant difference between EDS +I/R group and Cast +I/R group (P>0.05), but KIM-1 level in EDS+I/R group was lower than that in Cast +I/R group (P<0.05).After reper-fusion for 24 h, the levels of TST and LH in EDS +I/R group, Cast+I/R group and EDS+TST+I/R group were lower than those 1 h before operation (P<0.05).Compared with Cast+I/R and I/R group, the TNF-αlevel and expression of Fas mRNA and caspase-3 protein were significantly decreased in EDS +I/R group ( P<0.05 ) .CONCLUSION: EDS preconditioning substantially reduces the serum TST level , thus attenuating I/R-induced acute renal injury .TNF-α-induced Fas/FasL pathway may be involved in this process .

Objective To investigate the effects of cystectasia with sodium hyaluronate solution on ketamine related cystitis.Methods From June 2008 to October 2012,29 patients with ketamine related cystitis were analyzed,among which 27 were males and 2 were females.Their age ranged from 18 to 36 years old with a mean age of 25.All of them had frequency,urgency,urodynia and suprapubic pain.Voiding volume ranged from 10 to 160 ml and the interval duration ranged from 10 to 60 min.The test of ketamine in urine was positive.Patients were divided into four groups according to the treatment modality,namely the surgical treatment group (group A,n =11),surgery followed by addiction relapse group (group B,n =7),drug treatment group (group C,n =6) and non-drug treatment group (group D,n =5).Patients in group A and B underwent cystectasia with sodium hyaluronate solution under combined spinal-epidural anesthesia,and patients in group B were reported of addiction relapse within 2 weeks after cystectasia treatment.Patients in group C were free of the addiction to ketamine,while those in group D still rely on the ketamine.The average urine volume,OABSS and PUF scores were recorded 2 weeks and 4 weeks after the treatment.Results Two weeks after cystectasia,the average urine volums in group A and B were (107.7±39.6) ml and (95.0±35.5) ml respectively,which was larger than that in group D (42.0±13.5) ml,plus the volume in group A was larger than that in group C (63.3± 16.3) ml.The aforementioned differences were considered statistically significant (P＜0.05).As for OABSS and PUF scores,scores in group A [(6.0±2.6),(14.8± 4.2)] were lower than those in group C [(9.5±2.4),(22.5±2.2)].Furthermore,scores in group B [(9.0±2.4),(19.57±2.7)] were lower than those in group D [(12.2±1.9),(26.4±3.5)] (P＜0.05).Four weeks later,the average urine volume,OABSS and PUF scores in group A [(106.4±37.5) ml,(5.6± 2.5),(13.5±4.0)] and group C[(113.3±27.3) ml,(6.3±2.2),(14.5±2.7)] were significantly different from those in group B [(52.1±21.6) ml,(11.1±1.3),(26.4±2.8)] and group D [(40.0±13.7)ml,(12.0±1.6),(26.6±3.6)] (P＜0.05).While,no obvious distinction was observed between group A and group C,group B and group D in terms of average urine volume,OABSS and PUF scores at 4 weeks postoperatively (P＞0.05).Conclusions Cystectasia can efficiently alleviate lower urinary tract syndromes in patients with ketamine related cystitis.

Objective To analyze the relevant factors affecting prognosis of pulmonary infection after renal transplantation.Methods The clinical data of 40 patients who suffered from pulmonary infection after renal transplantation at the First Affiliated Hospital of Jinan University from January 2000 to December 2010 were analyzed retrospectively.By Cox risk model,single and multi-analysis were performed on 20 possible factors,including age,gender,time of infection,type of infection,white blood cell count,neutrophil ratio, hemoglobin,blood glucose,serum creatinine (Scr),pulmonary infection complicated with acute respiratory distress syndrome or acute pulmonary injury,rejection,blood transfusion,infusion of albumin,infusion of immune globulin,use of ventilator,way of offering oxygen,immunosuppressive regimen,dosage change of immunosuppressant,anti-infection therapeutic regimen and length of stay.Results and Conclusions Triple immunosuppressive therapy without mycophenolate mofetil (MMF ) and increase of neutrophil ratio were independent risk factors for pulmonary infection after renal transplantation.Triple immunosuppressive therapy with MMF combined with early anti-infection therapeutic regimen may improve patient and graft survival of patients with pulmonary infection after renal transplantation.

As a widely recognized public health problem as well as prevalent and challenging to modern society, chronic insomnia is involved in wide brain areas (such as prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, and thalamus) and emotion-cognition neuro-circuit. It is closely related to the conditioned hyperarousal and the increased information process and/or the impaired inhibitory ability to withdraw from awaking state. Thus, some specific abnormal mode may exist in the emotion-cognition circuit, which is associated with abnormal cognition load, such as repeated retrieval/intrusion of aversive memories during night. Studies through the combination of multiple techniques including psychology, electrophysiology and neuroimaging methods are needed to further enhance the understanding of chronic insomnia.
Brain ; physiopathology ; Electrophysiology ; Gyrus Cinguli ; Hippocampus ; Humans ; Neuroimaging ; Prefrontal Cortex ; Sleep Initiation and Maintenance Disorders ; pathology ; Thalamus

Conditioned fear and its abnormal extinction are involved in the psychopathology of anxiety disorders, such as posttraumatic stress disorder (PTSD). Cognitive enhancing agents have been demonstrated to alter fear extinction in many animal research literatures. The present review has examined the pharmacological role of gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid as well as compounds able to alter the epigenetic and neurotrophic mechanism in fear extinction, highlighting great hope for the future treatment of anxiety disorders with new agents based on the fear extinction.
Animals ; Anxiety Disorders ; drug therapy ; psychology ; Cannabinoids ; pharmacology ; therapeutic use ; Conditioning, Psychological ; drug effects ; Extinction, Psychological ; drug effects ; Fear ; drug effects ; psychology ; Humans ; Nootropic Agents ; pharmacology ; Stress Disorders, Post-Traumatic ; drug therapy ; psychology ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use

BACKGROUND: Shape memory polyurethane (SMPU) may be employed for bone repair capable of resisting stress shielding and bone non-union due to the shape memory effect responding to changed external temperature. Evaluating the cytocompatibility of SMPU is important for its further in vivo experiments and applications. However, few have been done to investigate the cytocompatibility of SMPU after encounted from deforming and shape recovering.OBJECTIVE: To evaluate the osteoblast compatibility of SMPU before and after stretching-shape recovering process. METHODS: Solvent casting method was used to fabricate SMPU films; the obtained SMPU films were stretched to 200%, and then fixed and finally recovered to its odginal shape at T_g+15 ℃, T_g-15 ℃ and T_g+15 ℃, respectively. Atomic force microscope (AFM) with tapping mode was employed to probe the surface morphology and phase separation of SMPU. Primary osteoblasts at 3-5 passages were seeded on SMPU films in vitro to evaluate the adhesion, proliferation and spreading of osteoblasts. RESULTS AND CONCLUSION: There were obvious and regular phase separation resulted from soft segments and hard segments in SMPU, and some groove-ddge architectures within a scale of micrometers were produced by the stretching-shape recovering process. These special micropatterned structures promoted osteoblast adhesion and proliferation, and also resulted in partially oriented cell growth along the grooves. Shape memory process, i.e. stretching-shape recovering process may obviously change the surface morphology of SMPU films, and suggesting better biocompatibility with osteoblasts.

Objective To explore the toxicity and safety of 32P-CP-PLLA seeds interstitial implantation. Methods 30 beagle dogs were randomly divided into 10 groups according to different drugs (32P-CP-PLLA and 32P-CP),different doses (185, 370 and 740 MBq) and different sites (gluteus and liver). At different time-points after surgery, the weights of dogs were measured. The blood routine and blood biochemical indexes,PC Ⅲ ,HA,CG,PCⅣ and LN were examined. ECT imaging was performed and histology was observed dynamically. Blood, urine and faeces were measured continuously for 12 weeks and 30 days, respectively. Results ECT imaging demonstrated in seed groups and 32P-CP muscle groups radioactivity concentrated continuously in the area of implantation, without liver imaging. 471.67 MBq/m2 of 32 P-CP was injected in liver,while the absorbed dose was 31 Gy,without significant liver damage. When the dose was 794. 28 MBq/m2 , the absorbed dose was 56 Gy,with strong liver and systemic toxicity. But implanting seeds at the same or higher dose, the absorbed dose was 89.83-178.68 Gy in the area of implantation, and the rest liver was 1.09-2. 18 Gy,without liver damage. Dogs in liver group died at 23, 29 and 45 d, respectively, and the inspections of liver fibrosis were higher than the means of the other groups.Blood routine and blood biochemistry indexes between the other groups showed no significant differences.Effective half-life of 32P-CP-PLLA was 11.78 d, while that of 32P-CP was 6. 82 d in liver, and 8. 73 d in gluteus. Mild to moderate injury were found in liver group at 4 weeks. Moderate to serious injury were found. Liver cell necrosis and proliferation were found at 4-6 weeks in other liver groups. In muscle groups,only cellular edema was found in muscle groups at 2 week. The radioactivity count rate in blood for seed groups showed slowly jagged decreasing over time, and decreased exponentially for 32PCP groups. The radioactivity count rate in urine and faeces were multi-peak descending in seed groups. Conclusions 32P-CP-PLLA seeds have the advantages of suitable target location, degradable, non-migration and easy to protection, and it could be used in treatment for different blood supply types of solid tumors. Liver of beagle dog could endure the dose from 32 P-CP-PLLA seed twice as 32P-CP lethal dose.