Objective To establish models of different susceptibility of heroin-induced conditioned place preference (CPP) in rats and investigate the relation between novel environmental response and heroin-dependent susceptibility. Methods After an open-field test, 70 male Sprague-Dawley rats were classified into 2 groups according to the numerical value of heroin-induced CPP, each accounting for 30%. The correlation between open-field test and CPP was analyzed. Results CPP value was much higher than pre-test scores in the rats after exposure to heroin (P<0.01). Compared with the low-CPP group, the high-CPP group had much higher scores in open-field test (P<0.01). The deviation of resident time at natural preference side tested and pre-tested had positive correlation with open-field test (P<0.05). Conclusion Heroin-induced CPP model of different susceptibilities could be successfully established by chronic heroin exposure. The novel environmental response is a reliable predictor for its vulnerability to develop heroin dependence.

Objective To establish the rats model of different susceptibility of heroin addiction,and to explore the possible dopamine D2 receptor (D2R) and dopamine transptor (DAT) mechanism leading to the different susceptibility. Methods 130 male SD rats were carried out CPP training,and the rats were randomly assigned into heroin exposure group (n = 100) and saline control group (SC, n = 30). Heroin exposure group were re-classified into two groups according to the numerical value of the CPP-Pre (the testing score minus that of the pretest):high preference group(HP group) and low preference group(LP group) ,each accounting for 30% of the total rats.The D2R and DAT protein expression of high and low preference group and saline control group rats were detectedwith immunohistochemical method in PFC at 30 minutes and on the 1st,3rd,7th, 14th days after the last injection(149.33 ±2.51 vs 135.83 ±1.78 vs99.33 ±2.84,141.83 ±2.50 vs 131.67 ± 1.87 vs99.17 ±3.61,132.83 ±2.40 vs 122.00 ±2.67 vs 100.33 ±4.26,125.67 ±2.22 vs 113.17 ±2.81 vs 98.33 ±3.25,116.86 ± 1.94 vs 108.63 ± 2.31 vs 98.17 ± 3.82 , respectively, P＜0.05). The D2R protein expressions of HP rats were significantly lower than those of the LP and control group rats (P ＜ 0. 05), and those of LP rat were than lower than those ferent among three groups on addiction phase and 1st,3rd days after the last injection of heroin respectively, respectively (P ＜ 0. 05). The DAT protein expressions of HP and LP rats were significantly lower than those of controlgroup rats (P＜ 0. 05). At all testing time-points, the DAT protein expressions had no significant difference betweenHP and LP group(P＞0. 05). Conclusion D2R and DAT of the rats show appears down-regulation in the PFC after chronic heroin exposure. Different individuals have different D2R sensitivity or receptor levels ,and lower D2R related to the high susceptibility to heroin. Susceptibility to heroin addiction may not be directly related to the expression of DAT.

Objective To explore the characteristic of memory impairment and its relationship with Nmethyl-D-aspartate receptor 2B (NR2B) expression in alcohol dependence patients,in order to provide an unprecedented view of alcohol-associated memory impairment therapy.Methods Participants (n=67) included 35 alcohol dependence patients and 32 matched healthy controls.Wechsler memory scale (WMS) was used to access the memory.The expression levels of NR2B were detected with quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results Compared with the memory quotient(MQ) of controls(69.45±8.96),that of alcohol dependence patients(50.59±8.64) significantly decreased (t=-6.08,P＜0.01).Compared with the NR2B expression level of controls (1.00-0.00),that of alcohol dependence patients (3.52 ± 1.17) significantly increased (t =9.67,P＜0.01).MQ was negatively correlated with the levels of NR2B expression (r=-0.44,P＜0.05).Conclusion Alcohol dependence patients suffer memory impairment detected by WMS,and modulate NR2B expression may improve the memory.

OBJECTIVEBy explore the role of serum soluble Fas (sFas) in occurrence and progression of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP).

METHODSEnzyme-linked immunosorbent assay (ELISA) was used to detect serum sFas levels in 40 patients with DEACMP in acute stage and convalescent stage, with 36 healthy elderly subjects as the control group.

RESULTSSerum sFas levels of the patients with DEACMP in both the acute and convalescent stages showed no significant difference from those in the control group (P=0.737 and 0.137, respectively), nor was any significant difference found between the patients in acute and exacerbation stages (P=0.059).

CONCLUSIONSerum sFas is not involved in the occurrence and progression of DEACMP.

Adult ; Aged ; Aged, 80 and over ; Brain Diseases ; etiology ; Carbon Monoxide Poisoning ; blood ; complications ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; fas Receptor ; blood

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.