Activation of the complement C3/C3aR pathway in the prefrontal cortex mediates methamphetamine addiction in rats / 中国药理学与毒理学杂志

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.

Alterations of regional homogeneity and interhemispheric voxel-mirrored homotopic connectivity in patients with methamphetamine dependence / 中华神经医学杂志

Objective:To investigate the differences of spontaneous neural activity and functional connectivity between bilateral symmetrical voxels in the local brain regions at resting-state of methamphetamine (MA) dependent patients and healthy controls (HCs).Methods:Forty-six MA-dependent patients, admitted to and received drug rehabilitation treatment for the first time in our hospital from February 2014 to October 2019, and 46 HCs matched with age, gender and education level during the same period were enrolled in this study. The resting state functional magnetic resonance imaging (rs-fMRI) data of these subjects were collected; the static and dynamic regional homogeneity (ReHo, d-ReHo) and static and dynamic voxel-mirrored homotopic connectivity (VMHC, d-VMHC) were used to evaluate MA-related alterations of brain spontaneous activity and interhemispheric functional connectivity. The correlations of brief psychiatric rating scale (BPRS) scores with above values in the brain regions with significant inter-group differences were analyzed.Results:As compared with the HCs, the MA-dependent patients had significantly decreased ReHo in the left medial orbitofrontal cortex (mOFC), and significantly increased d-ReHo in the left mOFC, left middle frontal gyrus, bilateral inferior frontal gyrus, left precentral gyrus and left postcentral gyrus ( P<0.05). As compared with the HCs, the MA-dependent patients had significantly decreased VMHC in the bilateral mOFC, precentral gyrus and postcentral gyrus ( P<0.05). The ReHo, VMHC, d-ReHo, and d-VMHC were not significantly correlated with total scores and each factor scores of BPRS, and total dose of MA (after removing outliers) in MA-dependent patients ( P>0.05). Conclusion:During resting state, MA-dependent patients show obvious abnormalities in the coordination and stability of spontaneous neural activity and the coordination of interhemispheric activity in local brain regions, especially in the mOFC; abnormal ReHo, d-ReHo and VMHC in left mOFC may be important neuroimaging biomarkers for MA-dependence.

Aberrant topology of functional networks in chronic methamphetamine-dependent patients / 中华神经医学杂志

Objective:To investigate the topological alterations of brain functional networks in patients with chronic methamphetamine (MA) dependence.Methods:Resting-state functional magnetic resonance imaging was used to map the brain networks of 46 patients with MA-dependence (MA group) and 46 healthy controls (control group). Statistical methods were used to compare the differences of brain functional connection and topological parameters between the two groups, and the correlations between these topological parameters with significant inter-group differences and clinical measurements were analyzed.Results:(1) Brain functional connection: as compared with the control group, the MA group had significantly enhanced functional connectivity in the subnetworks consisting of several brain regions, including the inferior parietal lobule, posterior central gyrus, lateral occipital cortex, ventromedial occipital cortex, orbital gyrus, anterior central gyrus, fusiform gyrus, superior temporal gyrus and thalamus; as compared with the control group, the MA group had significantly attenuated functional connectivity in the subnetworks consisting of several brain regions, the orbit frontal cortex, precentral gyrus, paracenter lobule, inferior temporal gyrus, fusiform gyrus, parahippocampal gyrus, superior parietal lobule, postcentral gyrus, medioventral occipital cortex, lateral occipital cortex and amygdala. (2) Network topology attributes: the brain functional networks in all subjects from the MA group and control group held worldlet; but attribute of worldlet in the MA group was significantly reduced as compared with that in the control group ( P<0.05); moreover, the MA group had significantly decreased clustering coefficient, local efficiency, and modularity as compared with the control group ( P<0.05). In terms of regional topological attributes, such as betweenness centrality, the MA group presented evident reduction in the left superior frontal gyrus, right orbit frontal cortex, right middle temporal gyrus and right/left lateral occipital cortex as compared with the control group with significant differences ( P<0.05). (3)Correlation analysis: the betweenness centrality of right middle temporal gyrus exhibited a positive correlation with the age of patients using MA for the first time ( r=0.327, P=0.028); a positive correlation was found between the modularity and activating factor scores in Brief Psychiatric Rating Scale (BPRS) in MA group ( r=0.315, P=0.035). Conclusions:Part of the global/local topological attributes of the brain functional network of patients with MA addiction are damaged. The younger the patients are when they take MA for the first time, the lower the betweenness centrality of the right middle temporal gyrus; the more the local attributes are damaged; and furthermore, the deeper the network modularity, the severer the active symptoms in the psychotic symptoms.

Association between sleep and leukocyte telomere length in middle-aged and older adults / 中华流行病学杂志

Objective To understand the association between peripheral leukocytes telomere length (TL) and sleep in middle-aged and old adults.Methods A total of 176 middle-aged and old adults were investigated by using the Pittsburgh Sleep Quality Index and questionnaire.TL was measured by fluorescence quantitative PCR.The correlation and regression analysis between sleep and telomere length was performed.Results TL had a mean T/S ratio of 0.995 ± 0.23.There was a negative correlation between TL and age (r=-0.241,P=0.003).With increasing age,sleep quality became worse (r=-0.230,P＜0.01),the time to fall asleep became longer (r=0.227,P＜0.01),sleep duration was shorter (r=-0.486,P＜0.01),sleep efficiency became worse (r=-0.226,P＜0.01).After controlling for the effects of gender,age,marital status,income level,residence,smoking,drinking,physical exercise and disease status,multiple linear regression analysis indicated that sleep quality (β3=0.057,P＜0.01),time to fall asleep (β =-0.046,P＜0.01),sleep duration (β3=0.086,P＜0.01) were independent influencing factors of telomere length,suggesting that the people who had better sleep quality,the shorter time to fall asleep,the longer sleep time would have longer telomere length.Conclusions Sleep is a relevant factor affecting TL in middle-aged and elderly population.Good sleep may delay aging by slowing TL.We encourage to conduct health education about the importance of sleep quality in community.

Association between sleep and leukocyte telomere length in middle-aged and older adults / 中华流行病学杂志

Objective To understand the association between peripheral leukocytes telomere length (TL) and sleep in middle-aged and old adults.Methods A total of 176 middle-aged and old adults were investigated by using the Pittsburgh Sleep Quality Index and questionnaire.TL was measured by fluorescence quantitative PCR.The correlation and regression analysis between sleep and telomere length was performed.Results TL had a mean T/S ratio of 0.995 ± 0.23.There was a negative correlation between TL and age (r=-0.241,P=0.003).With increasing age,sleep quality became worse (r=-0.230,P＜0.01),the time to fall asleep became longer (r=0.227,P＜0.01),sleep duration was shorter (r=-0.486,P＜0.01),sleep efficiency became worse (r=-0.226,P＜0.01).After controlling for the effects of gender,age,marital status,income level,residence,smoking,drinking,physical exercise and disease status,multiple linear regression analysis indicated that sleep quality (β3=0.057,P＜0.01),time to fall asleep (β =-0.046,P＜0.01),sleep duration (β3=0.086,P＜0.01) were independent influencing factors of telomere length,suggesting that the people who had better sleep quality,the shorter time to fall asleep,the longer sleep time would have longer telomere length.Conclusions Sleep is a relevant factor affecting TL in middle-aged and elderly population.Good sleep may delay aging by slowing TL.We encourage to conduct health education about the importance of sleep quality in community.

Research Progress on mechanism of ERK signaling pathway in drug addiction / 中国药理学通报

Drug addiction is a chronic relapsing brain disease. Repeated drug exposure can cause neuroadaptations in major brain circuitries,leading to compulsive drug consumption behav-ior and relapse after abstinence.Many studies have found that intercellular signaling cascades mediated central nervous system remodeling in the rewarding circuitry and addiction associated neuroplasticity of learning and memory are important molecular mechanism of drug addiction.Studies show that extracellular sig-nal-regulated kinase (ERK)is associated with drug-mediated psychomotor activity,rewarding properties and relapse of drug seeking behaviors.Therefore,this article has reviewed the role of ERK signaling pathway in drug addiction.Research on the role of ERK signaling pathway in drug addiction will provide im-portant theoretical foundation for in-depth understanding of the molecular mechanism of drug addiction and shine a light on new molecular targets and treatment strategies for drug addiction.

Progress in research of epigenetic mechanisms of drug addiction / 中国药理学与毒理学杂志

Drug addiction is a chronic relapsing brain disease that is characterized by compulsive drug use and persistence of drug craving. Drug abuse can lead to changes in the neuron structure and function of plasticity,alterations in molecules and cells,and ultimately to individual abnormal behavior. Current studies have found that epigenetic changes leading to the sustainability of gene expression is an important mechanism of drug addiction. In this review,we will systematically summarize the latest advances in epigenetic mechanisms of drug addiction. This review is expected to provide robust evidence that repeated exposure to drugs of abuse induces changes within the brain′s reward regions in three major modes of epigenetic regulation-histone modifications such as acetylation and methylation , DNA methylation,and non-coding RNAs. It promises a new perspective from which to gain insights into the genetic and epigenetic mechanisms of drug addiction and a new area for epigenetic research on clinical drug addiction treatment.

Nasal carriage and antimicrobial resistance of bacteria in health care workers in an intensive care unit / 中国感染控制杂志

Objective To evaluate nasal carriage and antimicrobial resistance of bacteria in health care workers (HCWs)in an intensive care unit (ICU),and provide basis for making prevention and control measures of health-care-associated infection(HAI).Methods From April 2014 to March 2015,nasal swabs from HCWs in ICU were collected,carriage and antimicrobial resistance of bacteria were detected.Results A total of 450 nasal swab speci-mens were taken,137 strains were isolated,isolation rate was 30.44%.There were no significant difference in na-sal carriage rates of bacteria in HCWs with different genders,ages,types of work,length of service,and education-al level (P >0.05);nasal carriage rates in HCWs at different seasons were significantly different (P <0.05 ).82 strains (59.85%)were gram-negative bacteria,the major were Klebsiella pneumoniae (21 .16%)and Enterobacter aerogenes (18.98%);55 strains (40.15% )were gram-positive bacteria,the major were Staphylococcus aureus (18.98%)and Staphylococcus epidermidis (15.33%).38 (27.74% )strains were multidrug-resistant strains. 7.69% (2/26)of Staphylococcus aureus were methicillin-resistant strains,3.45%(1/29)of Klebsiella pneumoniae and 3.85%(1/26)of Enterobacter aerogenes were imipenem-resistant strains.Conclusion Nasal carriage rate of bac-teria and detection rate of multidrug-resistant organisms in HCWs in ICU is high.

Levels of phthalate internal exposure levels in pregnant women and influencing factors / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the levels and influencing factors of phthalate internal exposure in pregnant women (gestation age ≤ 16 weeks).</p><p><b>METHODS</b>During April to June in 2013, 1 020 pregnant women (gestation age ≤ 16 weeks) who had established the maternal care manual were recruited in maternal and child health hospital of Siming District, Xiamen city. Participators were asked to complete a questionnaire to obtain information on socio-demographic characteristics, lifestyle behaviors, and antenatal examination and to provide a urine sample. Finally, 998 pregnant women who provided a urine sample and completed the questionnaire were enrolled. Adopting systematic sampling method, 100 ones were selected randomly among 998 pregnant women. High performance liquid chromatography-electrospray ionization-tandern mass was used to determine the concentration of five phthalate monoesters in each urine, including mono-n-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-ethylhexyl phthalate (MEHP). Based on the measurements and questionnaire data, multivariate logistic regression was used to analyze the association between the phthalate monoester levels and potential influential factors.</p><p><b>RESULTS</b>The detection rates of MMP, MEP, MBP, MBzP and MEHP in 100 pregnant urine samples were 94%, 93%, 87%, 83%, 99%, respectively. And the urinary median uncorrected concentrations of MMP, MEP, MBP, MBzP and MEHP in 100 urine samples were 20.56, 17.62, 10.15, 2.03, and 5.12 ng/ml, respectively. Specific gravity-corrected concentration were 20.81, 20.36, 12.88, 2.58, 5.00 ng/ml, respectively. The results of multivariate logistic regression analysis indicated that: education degree was negatively associated with urinary concentration of MMP, MEP, MBP, MBzP and MEHP, OR (95% CI) were 0.495 (0.253-0.966), 0.380 (0.191-0.755), 0.379 (0.186-0.774), 0.401 (0.196-0.819), 0.373(0.183-0.762), respectively. Participants who had hair permed and dyed during pregnancy had higher urinary level of MBP and MBzP, OR (95% CI) were 12.867 (1.240-133.525), 15.982 (1.367-186.911), respectively; Participants who use cosmetics during pregnancy had higher urinary level of MEP and MBP, OR (95% CI) were 2.977 (1.012-8.757), 4.440 (1.485-13.272), respectively; plastic bottled water consumption was positively associated with urinary concentrations of MEP and MEHP, OR (95% CI) were 3.780 (1.417-10.083), 2.699 (1.039-7.010), respectively; annual household income was negatively associated with urinary concentration of MMP, OR (95% CI) was 0.597 (0.372-0.959); individuals who took medications during pregnancy had higher urinary level of MEHP than non-takers, OR (95% CI) was 4.853 (1.084-21.732).</p><p><b>CONCLUSION</b>Pregnant women whose gestation age was less than 16 weeks are generally exposed to phthalate. Phthalate internal exposure levels are significantly associated with most measured factors and the influencing factors with different phthalates internal exposure levels are different.</p>

Infusion of clenbuterol into infralimbic cortex attenuates cue-induced reinstatement of heroin-seeking behavior / 中国药理学与毒理学杂志

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.

Study on the expression of aromatase P450, COX-2, ER and PR in adenomysis / 中国基层医药

Objective To investigate the expression and significance of aromatase P450,COX-2,ER and PR in the patients with adenomysis.Methods The immunohistochemistry staining was used to detect the expression of aromatase P450,COX-2,ER and PR in ectopic endometrium and eutopic endometrium of 30 patients with adenomyosis and 30 cases in control group.Results The expression of aromatase P450,COX-2 in ectopic endometrium were significantly higher than those in eutopic endometrium (all P ＜ 0.05) ; The expression of ER,PR in ectopic endometrium were significantly lower than those in eutopic endometrium (all P ＜ 0.05),excepted the expression of PR in eutopic endometrium,the expressions of both ER and PR lose their periodical cycle.There was positive correlation between the expression of aromatase P450 and COX-2 in adenomysis group(P ＜ 0.05).In adenomyosis,the expression of aromatase P450,COX-2,ER and PR in dysmenorrhea subgroup were significantly higher than those in non-dys menorrhea subgroup(all P ＜ 0.05).Conclusion Aromatase P450,COX-2 and ER play important roles in the genesis and development of adenomyosis and dysmenorrheal,PR is not the main pathogenic factors of adenomyosis.The expressions of aromatase P450,COX-2 and ER in adenomyosis have nothing to do with endometrial cyclical change and are not subject to the regulation of ovarian hormones.

Impact of pain care standard training on pain-related knowledge and attitude of junior nurses in orthopedics department / 现代临床护理

Objective To investigate the impact of pain care standard training on the pain-related knowledge and attitude of junior nurses in orthopedics department.Methods The standard pain care training was done for the junior nurses in the orthopedics department. The scores of questionnaires related to pain-related knowledge and attitude were collected and compared between pre-and post-training. Result There was significant statistical difference in the measurements related to the junior nurse’s knowledge and attitude between pre-and post-standard training(P<0.05).Conclusion The standard pain care training can enhance junior nurses knowledge,improve the attitude towards pain,and set up apporiate pain management behavior.

The substitution effect of nicotine in heroin discriminative rats / 中华行为医学与脑科学杂志

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.

Effect of Tongxinluo on Cerebral hemodynamics Carotid Artery Atherosclerotic Patients / 中国实用内科杂志

Objective To study the effect of Tongxinluo on Cerebral hemodynamics in Carotid attery alerosclerotio and Cerebral blood Shorty Suppeied patients.Methods eighty-three of Carotid artery in atheroseterotie and cerebral blood shorty supplied patients were lrealed with Tongxinluo Capsule four tablet,potid,The course of treatment was 8weeks. Changes of hemodynamics in patients with brain ischemic were examined before and after treatment,and compared with fifty old health paplpe.Results Average blood flow velocity increased significanily(P

Clinical Study of Granisetron Against Postoperative Nausea and Vomiting Under Patient Controlled Analgesisa / 中国药房

OBJECTIVE:To study the therapeutic effect of granisetron on postoperative nausea and vomiting(PONV) under patient controlled analgesia(PCA) and to observe the influence of infusion rate of granisetron on blood circulation during operation METHODS: 90 selective surgical patients were divided into 3 groups A group(control):ondonsetron 8mg;B group:tropiestron 3mg; C group:granisetron 3mg The solutions of granisetron hydrochloride were infusied at 20,30,40,50 and 60 min before the end of operation The change of the circulation condition and the status of nausea and vomiting were observed at infusion period and 4,8,12,24hs,2d and 3d postoperatively RESULTS:Under expansion of blood volume,if infusion duration was longer than 20 min for granisetron,the circulation condition(MAP,HR) were not affected during infusion period and no headache was found There were significant differences in PONV between group A and group B(P