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*

Objective To assess the safety of paliperidone palmitate(PP)injection versus other antipsychotic drugs long-acting injections(LAIs)in the treatment of schizophrenia.Methods PubMed,Web of Science,Embase,Cochrane Library,PsycINFO,CNKI,SinoMed,VIP and WanFang Data databases were searched to collect randomized controlled trials(RCTs)on PP injection versus other antipsychotic drugs LAIs in the treatment of schizophrenia from the inception to April 30,2023.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies.Meta-analysis was then performed using RevMan 5.2 software.Results A total of 12 RCTs involving 4 368 patients were included.The results of Meta-analysis showed that there was no significant difference in clinical efficacy between PP injection treated group and risperidone LAIs treated group(P＞0.05),no significant difference was found for positive and negative syndrome scale(PANSS)overall score changes between PP injection treated group and other antipsychotic drugs LAIs treated group(P＞0.05).Compared with other antipsychotic LAIs treated groups,PP injection treated group had a significantly higher rate of total withdrawls(RR=1.14,95％CI 1.06 to 1.24,P＜0.01)and the incidence of adverse reactions of abnormal injection site(RR=2.08,95％CI 1.03 to 4.22,P=0.04).Conclusion Current evidence indicates that PP injection didn't show significant difference in efficacy outcomes,while may increase the incidence of some adverse reactions when compared with other antipsychotic drugs LAIs for schizophrenic.However,due to the limitations of the quantity and quality of the included studies,the above conclusions still need to be validated by more high-quality studies.

Objective This study aimed to investigate the effects of Aβ3-10KLH active immunization on brain aging in the SAMP8 rapid aging mouse model using oxidative stress as the entry point.Methods SAMP8 mice were immunized with the Aβ3-10KLH vaccine,and a control group was established.Behavioral changes were observed using the Morris water maze test,and hippocampal morphological changes were examined using hematoxylin and eosin staining.The proportion of senescent cells in the hippocampus was detected using SA-β-gal staining.Biochemical kits were used to measure the changes in oxidative stress injury indicators malondialdehyde(MDA)and superoxide dismutase(SOD)activities to assess oxidative stress damage in the hippocampus.Results The Aβ3-10KLH vaccine attenua-ted cellular aging in the hippocampi of SAMP8 mice.It also improved memory ability(P＜0.05),ameliorated hippocampal tissue mor-phology,decreased the proportion of senescent cells in the hippocampus(P＜0.05),lowered MDA content(P＜0.05),and upregulated SOD activity(P＜0.05).Conclusion The Aβ3-10KLH vaccine significantly improves cognitive function in SAMP8 mice,slows down the aging of hippocampal neurons,and reduces oxidative stress damage.

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.

OBJECTIVE To s tudy the impr ovement effects of tilianin on the atherosclerosis （AS）model mice and its potential mechanism. METHODS Eight C 57BL/6J mice were taken as the normal group. Forty ApoE－/－ mice were randomly divided into model group ，tilianin low-dose ，medium-dose and high-dose groups [ 2.1，3.5，7.0 mg/（kg·d）] and simvastatin group [positive control drug ，3.5 mg/（kg·d）]，with 8 mice in each group. Normal group was given normal diet ，and other groups were given high-lipid diet to induce AS model. At the same time ，normal group and model group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，once a day ，for 12 consecutive weeks. The levels of TC ，TG， LDL-C，HDL-C，Ox-LDL，IL-1β，IL-6，MCP-1 and TNF-α in plasma were determined. The pathomorphological changes of the aorta in mice were observed. The positive rate of ICAM- 1，VCAM-1 and PCNA in the aorta were determined. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as protein expressions of TGF-β1，Smad2/3 and p-Smad 2/3 were also determined in aorta of mice. RESULTS Compared with normal group ，the plasma levels of TC ，TG，LDL-C，Ox-LDL，IL-1β， IL-6，MCP-1 and TNF-α in model group were increased significantly（P＜0.01），while HDL-C level was significantly reduced （P＜0.01）. Lipid plaques were formed in the aorta ，and the plaque area was large and caused severe stenosis of the lumen. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as positive rate of ICAM- 1，VCAM-1，PCNA and protein expression TGF-β1，Smad2/3，and p-Smad 2/3 in the aorta were significantly increased （P＜0.01）. Compared with model group ， most of above indexes of medication groups were improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Tilianin can inhibit the activation of TGF-β1/Smads signaling pathway and then inhibit the proliferation of vascular smooth muscle cells ，reduce ， inflammation and regulate lipid metabolism to inhibit the No.81960766） formation of AS.

OBJECTIVE：To s tudy the effects of Dracocephalum moldavica total flavonoids （TFDM）on AMPK/SIRT 1/PGC-1α signaling pathway ，and to explore the mechanism of its protective effect on myocardial ischemia reperfusion injury （MIRI）rats. METHODS：Totally 50 healthy male SD rats were randomly divided into sham operation group ，model group ，TFDM group [ 60 mg/（kg·d），by extract] ，Compound C+TFDM group [ig administration of 60 mg/（kg·d）TFDM+intravenous injection of 250 μg/kg Compound C（AMPK inhibitor ）via tail vein 15 min before reperfusion] ，EX-527+TFDM group [ig administration of 60 mg/ （kg·d）TFDM+ip injection of 5 mg/kg EX- 527（SIRT1 inhibitor）20 min before reperfusion] ，with 10 rats in each group. They were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. After last ig administration ，sham operation group underwent sham operation ，other 4 groups were established MIRI model by ligating left anterior descending coronary artery ， ischemia for 30 min and reperfusion for 2 h. After reperfusion ，the myocardial histopathological changes were observed by HE staining；RP-HPLC method was used to determine the contents of ATP ，ADP，AMP and NAD + in cardiac tissue. mRNA expressions of AMPK ，SIRT1 and PGC- 1α were detected by quantitative real-time PCR assay. Western blotting assay was the expressions of SIRT 1 and PGC- 1α protein in myocardium. RESULTS： Compared with sham operation group ， model group showed myocardial fib ers arranged disorder and horizontal stripes disappearance ，cell swelling burst and necrosis ，and nuclei deformation displacement ；the contents of ATP and NAD+，mRNA expression of AMPK ，SIRT1 and PGC- 1α，protein expression of SIRT 1 and PGC- 1α in cardiac tissue were decreased significantly （P＜0.05 or P＜0.01）；the contents of ADP and AMP ，the phosphorylation level of AMPK protein were increased significantly （P＜0.01）. Compared with model group ，myocardial pathological morphology were improved significantly in TFDM group ；the contents of ATP and NAD + in cardiac tissue ，mRNA expression of AMPK ，SIRT1 and PGC- 1α，the phosphorylation level of AMPK protein ，the protein expression of SIRT 1 and PGC- 1α were increased significantly（P＜0.05 or P＜ 0.01），while the contents of ADP and AMP were decreased significantly （P＜0.01）. Compared with TFDM group ，improvement effects of Compound C + TFDM group and EX- 527 + TFDM group on above indexes were reversed （P＜0.05 or P＜0.01）. CONCLUSIONS：TFDM may play a protective role on myocardium by activating AMPK/SIRT 1/PGC-1α signaling pathway and regulating energy metabolism.

Since February 9th, 2020, the mobile CT in Jianghan mobile cabin hospital had begun to be used for scanning patients with COVID-19.The mobile CT has played an irreplaceable role in clinical diagnosis with its unique advantages. During CT scanning, the technicians should not only ensure that the patients receive the radiation dose as low as possible, but also be aware of the importance of the infection prevention and control. Meanwhile, we need concern the technicians about the psychological problems and should take effective action when they occured.

Objective To investigated the effect of procyanidin (PC) on the expression of cysteine proteinase -3 (Caspase -3) in type 2 diabetes mellitus SD rats with focal cerebral ischemia. Methods Following the random principle, 40 healthy Sprague - Dawley (SD) rats were numbered sequentially and randomly divided to normal rats with focal cerebral ischemia group,type 2 diabetes mellitus SD rats with focal cerebral ischemia group,PC low/ middle/ high -dose groups,with 8 rats in each group. The type 2 diabetes mellitus - MCAO model was set up. The doses of PC for low,middle and high - dose groups were 50 mg/ kg,100 mg/ kg,200 mg/ kg. Immunohistochemistry method was used to measure the activity of Caspase - 3. Results Compared with that in the normal rats with focal cerebral ischemia group[(11. 42 ±2. 52)],the expression of Caspase -3 increased in the type 2 diabetes with ischemia group[(15. 00 ± 2. 38)](t = 2. 17,P < 0. 01). Compared with that in the type 2 diabetes with ischemia group,the expression of Caspase - 3 decreased in the PC groups[(9. 38 ± 2. 00),(7. 71 ± 1. 55),(6. 96 ± 1. 57)](t = 2. 86,3. 13,3. 36,all P < 0. 01),whereby the middle and high - dose groups showed more significant decrease (t = 1. 92,2. 03,all P <0. 01) and with no statistically significant difference between the two groups(t = 1. 13,P > 0. 05). Conclusion PC can decrease the expression of Caspase - 3 protein in type 2 diabetes mellitus SD rats with focal cerebral ischemia, finally may inhibit the apoptosis.

Objective To explore the influencing factors of patients with post-stroke depression (PSD) and study their impact on the quality of life.Methods Fifty-two stroke patients admitted to the First ospital of China Medical University from February 2015 to May 2015 were randomly selected for the study,and these patients did not suffer depression as evaluated by the depression rating scale.Their age,history of diseases,types of diseases,cause of illness,disease area and treatments were collected in detail.These patients were followed up for six month.The mental state was assessed by Hamilton depressive scale (HAMD) and self-rating depressive scale (SDS).The life quality was evaluated by stroke specific quality of life score (SS-QOL) and modified Rankin scale(mRS).These data were selected by stratified sampling method and analyzed by SPSS 17.0 software.Results The incidence of PSD in elder patients (≥ years) was significantly higher than in the younger patients (P ＜ 0.05).Patients with cardiogenic cerebral embolism are more likely to suffer from PSD (P ＜ 0.05).The patients with infarction in different regions have different probability to suffer from PSD.Those patients with cerebral infarction in basal ganglia exhibited more possibility on PSD than others (P ＜ 0.01).Previous disease,including hypertension,diabetes and coronary disease,had no effects on PSD.There were no significant effects of stroke types and thrombolytic therapy on PSD.PSD had an unfavorable effect on the life quality of the patients.Conclusion The patients with cerebral infarction in basal ganglia,aged over sixty and cardiogenic cerebral embolism are prone to PSD,and we should pay more attention to them.PSD has a negative impact on the quality of life of patients.

Objective To retrospectively study the clinical and electrodiagnostic features in subacute combined degeneration of spinal cord (SCD)patients. Methods The clinical and electrodiagnostic recordings of all SCD patients conformed in our Neurology Department from Janu?ary 2013 to July 2015 were retrospectively reviewed. Totally 29 patients diagnosed as SCD,whom received no treatment before admitted in our hos?pital,were recruited for the study. Correlation analysis between serum level of vitamin B12(VB12),course of disease and degree of neural lesion was performed,and the electrodiagnostic features were summarized and analyzed. Results The course of disease had significant correlation with the degree of neural lesion(P=0.001),but there was no significant relevance between serum VB12 level and neural damage(P>0.05). Electrodi?agnostic examination revealed:The abnormal rate of motor nerve(15.20%)was lower than that of sensory nerve(42.75%,P<0.001)and the up?per limb nerve(27.1%)was lower than that of lower limb nerve(30.87%,P=0.578). There was no remarkable difference of abnormal rate in all kinds of nerves of motor and sensory nerve(P1=0.320,P2=0.755). In the analysis of the parameters of electromyograph,there was statistical signif?icance of the abnormal rates of compound muscle action potential(CAMP)between each motor nerve(P=0.005). There was statistical signifi?cance of the abnormal rates of CAMP and no function between each sensory nerve(all P<0.001). Conclusion The course of disease has signifi?cant correlation with the degree of neural lesion. Sensory nerve is tended to be betreffend than motor nerve. Phil.always nervous are more likely to be affected than others in motor nerve at CAMP. Tibial nerve is easier to be influenced at CAMP in sensory nerve ,and the lesion is more serious.