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OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.
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Herpes simplex virus (HSV) is a double-stranded DNA enveloped virus that causes severe effects on the human body by infecting the skin and nerve tissues. Because of latency and reactivation, the rapid detection and eradication of HSV are great challenges for clinical treatments. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system has developed rapidly in the field of gene editing and detection due to its simple design and high targeting efficiency.
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Objective To investigate the endocytosis and exocytosis of soluble uranium in human kidney proximal tubular epithelial (HK-2) cells and the cytotoxicity after uranium exposure. Methods Cell Counting Kit-8 assay was used to determine the cell viability after different concentrations of uranium exposure, and optical microscopy and transmission electron microscopy were used to observe the changes in cells after uranium exposure. Inductively coupled plasma mass spectrometry was used to monitor the endocytosis and exocytosis of uranium over time by cells. Flow cytometry was used to assess the changes in cell cycle and apoptosis after uranium exposure. Results After uranium exposure, HK-2 cells showed dose-dependent damage; cell cycle was arrested in G1 phase; cell apoptosis and necrosis occurred; cell proliferation was inhibited. The content of endocytic uranium increased gradually within 24 h, and there was a threshold for uranium endocytosis, while the fraction of uranium binding to cell surface was low (< 0.2%). Over 40% of the endocytic uranium would be exocytosed within 1 h. Uranium could form needle-like precipitates in both intracellular and extracellular areas after uranium exposure. Conclusion After uranium exposure, cells show decreased viability, cell cycle arrest, and cell apoptosis. The process of endocytosis and exocytosis of soluble uranium is very rapid. HK-2 cells can convert soluble uranium into non-toxic precipitates.
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Uranium is an important radioactive actinide in nature and an important nuclear material in nuclear industry. After uranium is accidentally released into the environment, it enters the body through the respiratory tract, the digestive tract, and other ways, then enters the circulation system through blood, and is finally mainly deposited in the kidney and bone, causing a certain degree of toxicity. Therefore, efficient low-toxicity chelators are an important way to reduce radionuclide pollution, radiation damage, and chemical toxicity. This article reviews uranium deposition and harm, the detoxification mechanism of uranium chelators, and the research advances in uranium chelators and points out the development trend of uranium chelators.
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Objective:To analyze the application effect of cluster management measures in improving the quality of emergency medical treatment.Methods:By analyzing the problems existing in the work of emergency department, the cluster management scheme was formulated and the intervention measures were implemented from the aspects of intelligent information system, patient management system and medical service process. The accuracy and efficiency of emergency triage, the satisfaction of patients and medical staff, the incidence of medical complaints and disputes and the rate of sudden death were compared before and after cluster management.Results:Before and after the implementation of cluster management, the accuracy of triage classification was 95.0% and 98.7% respectively, and the triage time was (68.3±12.8) s and (50.5±7.2) s respectively( P<0.001). The satisfaction of patients, doctors and nurses increased, the number of complaints decreased from 15 to 5 in half a year, and the number of sudden death decreased from 39 to 23 with a significant difference( P<0.05). Conclusions:The application of cluster management measures in emergency management can improve the medical quality, the satisfaction of medical staff and patients, and ensure the safety of patients.
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Objective:To investigate whether peritoneal dialysis can replace hemodialysis as an option for urgent-start dialysis for elderly patients with end-stage renal disease who need emergency initial dialysis.Methods:This was a retrospective cohort study, with enrolment of patients ≥65 years with end-stage renal disease who started hemodialysis or peritoneal dialysis for the first time at the nephrology department of our hospital between January 1, 2013 and June 1, 2019 and were followed up regularly.All patients started dialysis within 5 days of catheterization.According to different dialysis methods, patients were divided into the urgent-start hemodialysis(USHD)group and the urgent-start peritoneal dialysis(USPD)group, and were followed up until December 31, 2019.Short-term(30 days after the procedure)dialysis-related complications and survival were compared between the two groups.Results:A total of 89 elderly patients with end-stage renal disease receiving urgent-start dialysis were included, with 40 cases in the USPD group and 49 cases in the USHD group.There was no significant difference in the incidences of infection-related complications(0.0% vs.2.5%), non-infection-related complications(2.0% vs.2.5%), re-catheterization(0 vs.0)and bacteremia(0 vs.0)between the two groups( P> 0.05). The Kaplan-Meier survival curve showed that the median survival times of patients with USHD and with USPD were 63.0 months and 38.0 months, respectively, with no statistical significance(Log Rank, χ2=0.025, P=0.88). The Charlson comorbidity index( HR: 1.205, 95% CI: 1.026-1.415, P=0.023)and albumin level( HR: 0.949, 95% CI: 0.903-0.997, P=0.037)were independent risk factors for the survival and prognosis of elderly patients with urgent-start dialysis.Furthermore, we stratified and made an interactive analysis of the albumin level and the comorbidity index of elderly patients with urgent-start dialysis and found that there was no significant difference between the two modes of dialysis in the survival rate of elderly patients with end-stage renal disease( P>0.05). Conclusions:It is safe and effective to start dialysis within 5 days after peritoneal dialysis catheterization.For elderly patients with end-stage renal disease, peritoneal dialysis can replace hemodialysis as an option for urgent-start dialysis.
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OBJECTIVE@#To analyze the clinical characteristics and treatment outcomes of the first episode of peritoneal dialysis-associated peritonitis (PDAP) in patients receiving long-term peritoneal dialysis.@*METHODS@#The clinical data of patients with the first episode of PDAP in 4 general hospitals in Jilin Province from 2013 to 2019 were collected retrospectively. According to the duration of dialysis, the patients were divided into long-term (≥36 months) and short-term (< 36 months) dialysis groups for comparison of the clinical data, treatment outcomes and long-term prognostic events.@*RESULTS@#A total of 625 patients with PDAP were enrolled, including 93 on long-term and 532 on short-term dialysis. Compared with those on short-term dialysis, the patients on long-term dialysis had significantly higher hemoglobin levels and lower glomerular filtration rates when the first episode of PDAP occurred (@*CONCLUSIONS@#Compared with those on short-term dialysis, patients on long-term dialysis are prone to gram-negative bacterial infection when the first episode of PDAP occurs with worse treatment outcomes but similar long-term outcomes. Long-term dialysis is an independent risk factor of extubation and treatment failure for the first episode of PDAP, and fungal and mixed bacterial infections are independent risk factors for treatment failure of the first PDAP in patients with long-term dialysis.
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Humans , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Peritonitis/etiology , Retrospective Studies , Treatment OutcomeABSTRACT
Objective To evaluate the applicability of the Critical Care Pain Observation Tool (CPOT) in medical patients with mechanical ventilation. Methods A descriptive design was chosen for this study. A convenience sample of 110 medical patients with mechanical ventilation in ICU was selected, among which, 53 cases were sober (including 34 patients with pain and 19 patients without pain), 57 cases were non-sober. The CPOT was applied for evaluating the reliability, validity, reactive degree, sensitivity, specificity and ROC curve analysis. Results Cronbach alpha coefficient was 0.865. Intraclass correlation coefficient was 0.883. CVI was 1.00. Spearman correlation with Visual Analogue Scale (VAS) was 0.544. In known-group technique, only pain score was statistically significant in Ramsay score. In reactive degree, score was statistically significant in three testing points. The CPOT had a sensitivity of 94.1％and a specificity of 46.7％. The area under the ROC curve was 0.716. Conclusions The CPOT has good internal consistency, interrater reliability, content validity, reactivity, moderate criterion validity. Speciality in distinguishing pain and other symptoms is worse. Future research is warranted to further verify the applicability of the CPOT.
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Objective To explore the feasibility of oxygen saturation related diffusion index for assessing oxygenation status,and to establish the critical value of the oxygen saturation related diffusion index,so as to provide more approaches to monitoring oxygenation status.Methods A total of 30 patients with acute respiratory distress syndrome (ARDS) receiving mechanical ventilation support were retrospectively reviewed.Totally 340 cases were collected at corresponding time points,and were divided into mild,moderate and severe groups according to ARDS Berlin criteria.Results There was a positive correlation between oxygen saturation related diffusion index and oxygenation index (r=0.698,P＜0.001);the critical value between the moderate and severe groups of oxygen saturation related diffusion index was 171(sensitivity 84.7％,specificity 68.2％),and the critical value between mild group and moderate group was 440 (sensitivity 56.9％,specificity 91.9％).Conclusion The oxygenation index was consistent with the oxygen saturation related diffusion index in judging the oxygenation status of ARDS patients.As a noninvasive and continuous index,the oxygen saturation related diffusion index provides a new method for nursing assessment.
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Objective@#To analyze the key issues and future trend of international intensive nursing.@*Methods@#The cluster analysis was adopted to analyze the intensive nursing literature in PubMed from 2010 to 2017.@*Results@#A total of 2 096 articles published in 367 journals from 34 countries were included. The research fronts from 2010 to 2017 focused on five aspects including quality management, mental problems, evidence-based nursing, healthy knowledge and attitude and practice, family′ participation in nursing, etc.@*Conlusion@#Researches on quality management, mental problems, evidence-based nursing, healthy knowledge and attitude and practice, family′ participation in nursing could provide references for related researches in China.
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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.
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Objective To establish a practicable and easily mastered emergency department overcrowding (EDO) assessment system suitable for domestic ED setting by determining the validity and usefulness of the national emergency department over-crowding study (NEDOCS) tool in a 2000-bed tertiary care academic institution in China in comparison with visual analogue scale (VAS) in order to address the worldwide grave concern of EDO.Methods In a period of 6 months,data of subjective and objective EDO assessed simultaneously three times a day (1:00,9:00,17:00) were collected.The data were analyzed by using Bland-altmann method and Kappa test to determine the coincidence between VAS and NEDOCS assessments.Results The VAS-p value evaluated by physicians was significantly lower than VAS-n value evaluated by nurses [(6.49 ± 1.82) vs.(7.12 ± 1.78),P ＜ 0.01].The reliability analysis showed that Kappa value was as low as 0.112 (P ＜0.01) suggesting there was a great discrepancy between VAS-p value and VAS-n value.VAS-m (average value of VAS-p and VAS-n) was taken for comparing different evaluation systems.The significant correlation was found between the VAS-m and NEDOCS (r =0.7l4,P ＜0.01).However,the Bland-Altman plot showed the 95％ limit of coincidence was in an extensive range (-32.47 to 71.42) suggesting discrepancy existed between two methods.Conclusions The present study suggested there was a significant discrepancy between the two subjective assessments of ED crowding (VAS-p vs.VAS-n).There might be a fatal flaw existed in the assumptions of the original VAS method for EDO measurement.Using the Bland-Altman plot analysis,the results showed that NEDOCS did not authentically reflect the staff' s sense of overcrowding in the ED.It is very important and urgent to establish an objective and effective EDO evaluation system for ED management.
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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.
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Basic and cIinicaI studies demonstrate that depression is associated with abnormaI neuraI pIasticity in some brain regions,incIuding the prefrontaI cortex and hippocampus. Brain-derived neurotro-phic factor(BDNF)and its signaIing pathways pIay a cruciaI roIe in reguIating neuraI pIasticity and deveI-opment of depression. Ketamine or scopoIamine can produce a quick and sustained antidepressant effect,and both can quictIy activate BDNF-signaIing pathways reIated to neuraI pIasticity. In order to pro-vide the theoreticaI basis for future researches on new antidepressants,the neuraI pIasticity mechanisms of faster-onset antidepressants are reviewed in this paper.
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ObjectiveTo evaluate the discriminative stimulus effects of nicotine on the basis of a rat model of heroin discrimination.MethodsMale Sprague-Dawley rats were trained to discriminate 0.3 mg/kg heroin from saline under a fixed-ratio (FR10) schedule of food reinforcement.After training,different doses of heroin and nicotine were used to substitute for training dose of heroin,the dose-response curve for heroin and the discriminative stimulus effects of nicotine were identified in rats.ResultsAll rats reliably discriminated 0.3 mg/kg heroin from saline.Different doses of heroin ( 0.03,0.1,0.3,0.56 mg/kg ) produced ( 33.9 ± 15.0 ) ％,( 43.3 ± 13.3 ) ％,(98.7 ± 0.5 ) ％,(99.4 ± 0.2 ) ％ total responding on heroin associated lever,heroin at the doses of lower than 0.3 mg/kg produced the dose-dependent relationship in heroin-appropriate responding.In heroin-trained rats,nicotine at the dose of 0.03,0.1 mg/kg produced(1.9 ±1.1)％,(13.7 ±5.6)％ total responding on heroin associated lever,there were extremely significant differences with 0.3 mg/kg heroin control (P＜0.01).However,nicotine at the dose of 0.3,0.5 mg/kg produced ( 60.4 ± 16.1 ) ％,(65.9 ± 16.4) ％ total responding on heroin associated lever,there were no significant differences with 0.3 mg/kg heroin control (P＞ 0.05 ).ConclusionNicotine at the dose of 0.3,0.5 mg/kg can partially produce heroin-like discriminative stimulus effects.
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0bjective To observe the different brain activation of acupuncture and electroacupuncture on healthy subjects and healthy subjects.Methods The different brain activation involved in heroin addiction between healthy subjects and addicts was detected by fMRI.Acupuncture point used in present study Was Zusanli (ST 36).Results Different brain activations between healthy subjects and addicts during electroacupuncture were hypothalamus(X0,Y2,Z9,t=7.36,P<0.01),anterior cingulate(X5,Y49,Z8,t=4.11,P<0.01),tempo-ral gyrus(X61,Y12,Z8,t=3.05,P<0.01).The difference of activated regions during conventional acupuncture between healthy subjects and heroin addicts was thalamus(X2,Y16,Z12,t=2.87,P<0.01),parahippocampus (X17,Y52,Z3,t=3.14,P<0.01),and hypothalamus(X0,Y2,Z9,t=6.98,P<0.01).Conclusion Regions with significant activation detected by fMRI are different during acupuncture in heroin addicts and in the healthy subjects.Notably,the hypothalamus activation is more robust in the addicts than in the healthy subjects during ac-upuncture stimulation.
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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.
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0.05);the infection rate of incision in study group(1.28%)was lower than that in control group(10.26%) significantly (P
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Daphnetin, isolated from Daphne koreane Nakai, has been reported to dilate blood vesse ls, inhibit thrombosis and have antiinflammatory effect. In this study, type Ⅰ and type Ⅱ protcin kinase A partially purified from rat skeletal muscle and protein kinase C from rat brain were incubated with varying concentrations of daphnetin. Type Ⅱ protein kinase A was siguificantly inhibited by daphnetin at the concentration of 0.0056?mol/L, while type Ⅰ protein kinase A and protein kinasc C were inhibitcd at the concentrations of 5.6?mol／L and 56 ?mol/L, respectively. The results indicated that daphnetin might be used as a specific inhibitor of type Ⅱ protein kinase A
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Intracellular [Ca+ + ]i was examined using Quin-2. Resting [Ca+ + ]i in platelets loaded with Quin-2 in media containing either 1 mmol/L CaCl2. or 2 mmol/L EGTA was 52.1?5.2nmol/L, 28.4+5.1 nmol/L, respectively. The concentration of external calcium appears to play an important role in cytosolic Cat++ hemeostasis in platelets. Stimulation with A2 3187( 25nmol/L ) caused [Ca++]i to peak at 145?30.8 nmol/L in the presense of extracellular 1mmol/L CaCl2 and 34.4?2.4 nmol/L after addition of 2 mmol/L EGTA. These data suggested that the most of this rise results from calcium entry across the plasma membrane, with a small contribution to the discharge of intracellular pool of Ca++.Anisodamine ( 100?mol/L ) had no effects on resting [Ca + + ]i and A23187-evoked [Ca++]i level in the absence of CaCl2, Anisodamine ( 100?mol/L, 25?mol/L), verapamil ( 10?mol/L ) decreased the A23187 -evoked [Ca++ ]i rises in the presence of CaCl2 by 38%, 34%, 25%, respectively. These results provided a mechanism for the calcium antagonistic effects of Anisodamine.