People departure from the treatment, prevention and health care purposes, intermittently or continuously excessive use of drugs with dependence, will cause serious mental and physical damage, while serious social harm.Opioids are the most commonly abused drug, abusers by taking an excess number of pills orally or by crushing the pills, followed by smoking, snorting, or injecting the new altered formulation to get euphoric.The escalating abuse of opioids has recently spawned the development of novel drug formulations resistant to various methods of tampering and misuse.This article discusses available opioids that include abuse-deterrent mechanisms as well as such agents currently in development.

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BACKGROUND: There is still no satisfactory therapy for thetreatment of cerebral infarction at present. Although sub-hypothermia is effective in the treatment of cerebral infarction, its side effect is relatively more. Local sub-hypothermia might have favorable effects in the treatment of cerebral infarction.OBJECTIVE: To observe the protective effects of local sub-hypothermia on the ischemic brain tissues in rats to further explore its mechanism.DESIGN: A randomized controlled basic study based on the experimental animals.SETTING: Institute of neurology of a university hospital.MATERIALS: The study was conducted in the Animal Laboratory of Neurology, the First College for Clinical Medicine, Harbin Medical University between April 2000 and January 2002. Fifty male Wistar rats(cleanness grade) with a bodyweight of(250 ± 25) g were selected.INTERVENTIONS: Ten rats were randomly selected from the 50 rats and divided into normal group and sham-operation group with 5 rats each. The rest 40 rats were randomly divided into normal temperature cerebral ischemia group and local hypothermia cerebral ischemia group with 20 rats each. Rat cerebral middle-sized arterial ischemia model was established for local sub-hypothermia disposal.MAIN OUTCOME MEASURES: Impacts on cerebral infarction volume,nerve function, and neuron-specific enolase(NSE) of rats in each group.RESULTS: The cerebral infarction volume at 48 hours after embolism in rats was ( 128.95 ± 13.42) or (84.90 ± 11.36) mm3 respectively, nerve function evaluation was( 1.60 ± 0. 24) or (0. 95 ± 0. 17), and serous NSE concentration was(13.55±4.07) or(9.19±3.42) μg/L in either sub-hypothermia group or normal temperature group, which were significantly different from each other.CONCLUSION: Local sub-hypothermia therapy has protective effects on ischemic cerebral neurons.

Objective To investigate the value of DNA-image cyt-ometry (DNA-ICM) in the diagnosis of urothelial cell carcinomas (UCC). Methods Totally 162 voided urine specimens (92 cases from urothel-ial car-cinomas patients and 70 cases from benign urinary system diseases patients ) were detected with DNA-ICM and liquid-based cytology (LBC), respectively. Results The sensitivity and specificity of DNA-ICM were 65.2%and 100% respectively in the diagnosis of UCC but those of LBC were 27.2% and 98.6%, respectively. The sensitivity of DNA-ICM was significantly higher than that of LBC in the diagnosis of UCC (P < 0.01). The sen-sitivity of DNA-ICM in upper urinary tract urothelial cell carcinomas (UTUC) were 77.1%, which was much higher than that in bladder urothelial cell carcinomas (57.9%) but no statistical significance was found (P >0.01). Conclusion DNA-ICM, which improves the positive rate of urinary cytology, has great application value in the diagnosis of urothelial cell carcinomas and it is an effective screening method for urothelial cancer in diag-nosis and follow-up.

Objective To observe the effect of traditional Chinese drug combined with training of musculus quadriceps fexoris on knee osteoarthritis(KOA).Methods70 out-patient clinic KOA patients were divided randomly into the Chinese drug group and control group with 35 cases in each group.The Chinese drug group was treated with Shentongzhuyu medicinal broth PO bid;the control group was treated with Sulindac 0.2 g PO bid.Two groups were combined with the training of musculus quadriceps fexoris,having 10 times per course and 3 courses in total with a 3 days interval between two courses.The therapeutic effect was evaluated with footplate pressure gait analysis and modified JOA marks.ResultsAfter treatment,the effect of the Chinese drug group was superior to the control group(P<0.05),especially 12 weeks post treatment.There maximum weight loading,time integral and weight loading intergral of affected limb of the Chinese drug group significantly improved after treatment(P<0.01),but for the control group,only weight loading intergral improved(P<0.05).ConclusionTraditional Chinese drug combined with training of musculus quadriceps fexoris has better curative effect on the pain and functional disturbance of KOA.

Objective To investigate the role of autophagy and synaptophysin (SYP) in cognitive impairment in de?pressed rats receiving electroconvulsive shock (ECS). Methods Clean and healthy adult male Sprague-Dawley rats were acclimatized to a standard laboratory environment for 7 days. The chronic unpredictable mild stress (CUMS) was used to establish the rat model of depression. Behavior tests were conducted before and after CUMS to evaluate the depression and cognition level of rats. After establishment of the model, 24 rats were randomly divided into ESC group (group E) and depression group (group D) with 12 rats in each group. The rats in group E were administered 80 mg/kg of propofol (10 mg/mL) by intraperitoneal injection, followed by ECS treatment. The rats in group D were administered propofol by intra?peritoneal injection, followed by sham-ECS treatments. The above interventions were conducted daily for 7 consecutive days. After the interventions, rats underwent behavior tests as before. Subsequently, rats were killed and specimens were collected for measurements. Immunohistochemistry was performed to examine autophagy markers such as Beclin 1 and LC3Ⅱand ELISA was used to detect SYP in the hippocampus. Results Group E after ECS significantly increased the percentage of sucrose preference (68.2%±8.7%), rearing times (7.0±1.9), total horizontal distance [(569.5±70.0) cm], es? cape latency [(21.9±5.3)s] and space exploration time [(20.5±3.9)s] compared with group D or group E before ECS. There was no significant difference in these index between groups before ECS or in group E between before and after ECS(P>0.05). Compared with group D, group E had upregulated protein expression levels of Beclin 1 and LC3Ⅱin CA1, CA3, DG as well as the area near the hippocampus and increased SYP contents (P<0.05). Conclusions Cognitive impairment in depression rats following ECS correlates with activated autophagy and increased SYP by ECS.

Objective To evaluate the changes in the expression of CXCR3 in regulatory T cells (Tregs) in the renal tissues of mice with renal ischemia-reperfusion (I/R) injury .Methods Forty-eight SPF male C57BL/6J mice ,aged 8-12 yr ,weighing 20-25 g ,were randomly divided into 3 groups ( n=16 each ) using a random number table:sham operation group (group S) ,group I/R and CD25 monoclonal antibody PC61 group (group P) . Bilateral kidneys were exposed and their pedicles were occluded for 45 min with atraumatic mini-clamp followed by 72 h reperfusion .PC61 250 μg was injected intraperitoneally at 24 h before the model was established .Blood samples were collected from the inferior vena cava at 24 and 72 h of reperfusion (T1 ,2 ) for determination of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations .Bilateral kidneys were obtained for determination of CD4+ CD25+ Foxp3+ Treg count and CXCR3+ CD4+ CD25+ Foxp3+ Treg count in renal tissues and the pathological changes of the kidney were scored .Results Compared with group S , the serum BUN and Cr concentrations and pathological scores were significantly increased at T1 ,2 in I/R and P groups ,and the number of CD4+ CD25+ Foxp3+ Treg and CXCR3+ CD4+ CD25+ Foxp3+ Treg was increased at T2 in I/R group ( P<0.05) .Compared with group I/R ,the serum BUN and Cr concentrations and pathological scores were significantly increased at T2 ,and the number of CD4+ CD25+ Foxp3+ Treg and CXCR3+ CD4+ CD25+ Foxp3+ Treg was decreased at T2 in P group ( P<0.05 ) .Conclusion Up-regulation of CXCR3 is helpful in migration of Tregs into the renal tissues of mice with renal I/R injury .

Objective To investigate the effect of growth inhibition and apoptosis induction of sunitinib-liposome-loaded microbubbles on renal carcinoma cell strain.Methods GRC-1 cell strain was cultured in vitro,and was divided into 6 groups:blank control group,pure microbubbles group,pure lipsomes group,sunitinib group,sunitinib-liposome-loaded microbubbles without ultrasound treat group,sunitinib liposome-loaded microbubbles with ultrasound treat group.Growth inhibition in different groups was observed at different time with MTT assay,apoptosis induction with Sigma-FlTC technology and transmission electron microscope.Results The growth inhibition and apoptosis promotion of GRC-1 cell were significantly increased in sunitinib-liposome-loaded microbubbles with ultrasound treat group compared to the other groups.Conclusions Microbubble guided sunitinih delivery can increase the effect of the growth inhibition and apoptosis induction of GRC-1 cells,which may provide an more effective approach for cancer treatment.

Objective To investigate the functional changes of dendritic cells (DC) in elderly patients with sepsis. Method Elderly patients (n = 20), ages 75 to 86 years, treated in the department of internal medicine for cadres and the medical intensive care unit (MICU), were selected to participate in the study. Patients with ma-ligoant tumors, hematological diseases, immune diseases, or a history of receiving drugs known to interfere with immune functions were excluded. Using the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) definition of sepsis, the patients were categorized into four groups: non-sepsis (group A) (n = 5) ; sepsis (group B) (n = 5) ; severe sepsis (group C) (n = 5) ; and septic shock (group D) (n = 5). The peripheral blood mononuclear cells (PBMCs) of each patient were isolated and cultured with human re-combinant granuloceyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in vitro for 10 days. The cells were examined under an inverted microscope, scanning electron microscopy, and flow cytometry. The MTT colorimetric assay was used to observe the abilities of the dendritic cells to stimulale an allogeneic T lym-phocyte response in vitro. Paired t -test was used to compare changes in the surface markers among the different groups, Results The PBMCs in the four groups of patients differentiated into cells with typical dendritic configura-tions after in vitro cuhure with combined cytokines. The CD40, CD80, CD86, and HLA-DR expressions on the cell surfaces increased after culture,with (43.2±12.5)%/(27.3±9.3)%, (31.4 ± 10.1)%/(22.5 ± 8.7)%, (39.3±15.7)%/(21.9±7.7)%, and (75.4±25.6)%/(58.7±16.7)%, respectively. The stimulation index (the abilities of the dendritic cells to stimulale the allogeneic T lymphocyte response in vitro) in the four groups of patients after culture were (23.3±7.9) in group A, (18.9±8.3) in group B,(11.4±5.1) in Group C,and (5.5 ± 3.7) in Group D. Conclusions The immune functions of the dendritic cells of elderly patients with sepsis decrease in a linear manner with the severity of their septic state.

Objective To investigate the protective effect of local mild hypothermia on the ischemic cerebral tissues. Methods A model of middle cerebral artery occlusion was prepared in Wistar rats to compare the difference of the cerebral infarction volume and neurologic function and the serum concentration of neuron-specific enolase (NSE) between the local mild hypothermia group and the normal temperature group. Results It was found that the cerebral infarction volume was 84.90?11.36 and 128.95?13.42 mm 3 in the local mild hypothermia group and the normal temperature group, the neurologic function score 0.95?0.17 and 1.60?0.24, and the serum concentration of NSE 9.19?3.42 and 13.55?4.07ng/ml,respectively. The differences between the two groups were statistically significant. Conclusion The findings of this study suggest that the local mild hypothermia treatment exerted protective effect on the ischemic neurons.