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*

Based on the data of a national sampling survey, this paper described and analyzed the understanding, attitude, behavior, and their differences and influencing factors of Chinese medical researchers on ethical review of biomedical research involving human subject. The survey found that researchers with master’s degree or below, working in scientific research institutes or universities, no overseas experience, living in the central region and not serving as committee members have relatively poor acquaintance of "ethical review" ; researchers with the characteristics of male, the younger age, living in the western region, knowing less about "ethical review" , agree more with the view that "ethical review consumes too much time and energy" ; researchers who serve as members of the ethics committee are more likely to participate in scientific research projects that have not passed the ethical review process. Therefore, recommendations are put forward: comprehensively popularizing the training of ethical review, focusing on strengthening the vulnerable groups and regions, strictly implementing ethical review laws and regulations, and strengthening evaluation and supervision, so as to improve the service quality and efficiency of ethical review in multiple directions.

BACKGROUND:Mesenchymal stem cells are susceptible to senescence during in vitro expansion,which greatly hinders their application in vivo and in vitro.How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE:To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS:Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method.Passage 2 cells were selected as normal control group.Passage 7 and later algebraic cells were selected as aging model group.Vascular endothelial growth factor(50 μg/L),basic fibroblast growth factor(10 μg/L),and their combination were administered.Cell proliferation was detected by CCK-8 assay.Cell senescence was observed by β-galactosidase activity staining.Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining,respectively,and the levels of senescence-related genes P16,P21,and P53 were detected by qRT-PCR.Gene expression levels of P16,P21,and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION:(1)Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells,which began to enter the plateau stage on day 9,and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9(P<0.05).(2)The phenotypic markers of the cells in the combined intervention group did not change,and the cell morphology changed from broad to slender.(3)Compared with the model group,the positive rate of β-galactosidase was significantly decreased(P<0.01);the number of nuclei increased(P<0.001);the total area of cytoskeleton increased(P<0.01);colony formation ability was enhanced(P<0.05);expression level of P16 was decreased(P<0.01)in the combined intervention group.These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype.

Placental diseases may affect the outcome of pregnancy and long-term health of the mother and fetus. Fetal fraction is a key indicator for the success of non-invasive prenatal testing, and has been associated with gestational age, body mass index and fetal chromosomal aneuploidies. Many studies have found that fetal fraction is also related to placenta-derived diseases and may become a new predictor for such diseases. This article has summarized the association between the two, with an aim to provide new ideas for the prediction of placental diseases.

Objective To investigate the improvement effect and related mechanism of roxadustat on myocardial ischemia-reperfusion(I/R)injury in mice.Methods Twenty four male C57BL/6N mice were randomly divided into the sham operation group,the control group and the roxadustat group,with eight mice in each group.A mouse myocardial I/R model was established.The control group was given 100 μL saline injection containing 5%dimethyl sulfoxide by gavage.The roxadustat group was given 25 mg/kg roxadustat by gavage.The left anterior descending coronary artery of mice in both groups was ligated for 40 minutes,and then reperfusion for 24 hours to establish the myocardial I/R model.In the sham operation group,only the left anterior coronary artery was pierced without ligation.The area of myocardial infarction in mice was detected by triphenyltetrazolium chloride(TTC)staining.The apoptosis of mouse cardiomyocytes was detected by TdT-mediated dUTP nick and labeling(TUNEL)staining.The expression of apoptosis-related proteins bcl-2 associated X protein(Bax),Caspase3 and inflammatory cell markers F4/80 and myeloperoxidase(MPO)were detected by immunohistochemistry staining.The damage of myocardial cells was observed by hematoxylin-eosin(HE)staining.Results The area of myocardial infarction after myocardial I/R was reduced in the roxadustat group compared to the control group and the sham operation group(P＜0.05).The number of apoptotic cells was higher in the control group and the roxadustat group than that in the sham operation group,and the number of apoptotic cells was lower in the roxadustat group than that in the control group(P＜0.05).The expression levels of Bax and Caspase3 proteins in myocardial tissue were higher in the control group and the roxadustat group than those in the sham operation group,while those of the roxadustat group was lower than those of the control group(P＜0.05).The expression levels of F4/80 and MPO proteins in myocardial tissue were lower in the roxadustat group than those in the control group(P＜0.05).In the control group,the myocardial tissue arrangement was disordered,and there was an increase in interstitial vacuoles.Compared with the control group,the myocardial cells were arranged more neatly in the roxadustat group,and the interstitial vacuoles were reduced.Conclusion Roxadustat can reduce the myocardial infarction area after I/R injury,inhibit myocardial cell apoptosis,alleviate myocardial injury,reduce infiltration of myocardial macrophages and neutrophils,and reduce inflammatory injury.

Objective:To investigate the status of nursing practice and organizational management for reperfusion therapy in ischemic stroke across medical institutions in Beijing.Methods:In June 2023, a survey was conducted among nursing managers from 62 medical institutions under the jurisdiction of the Beijing Stroke Treatment Quality Control and Improvement Center. The survey aimed to assess the current nursing practices and organizational management for reperfusion therapy in ischemic stroke.Results:Among the 62 medical institutions, 16.13% (10/62) had dedicated reperfusion therapy nurses for stroke, and 87.10% (54/62) had established specific nursing protocols and procedures for stroke reperfusion therapy within their departments. However, 27.42% (17/62) of these institutions based the development and updates of their protocols on experiential summaries rather than standardized guidelines. In terms of nursing practice, there was room for improvement in emergency identification and triage of suspected stroke patients, assistance with intravenous thrombolysis, patient condition monitoring, early rehabilitation, and related health education. Regarding nursing quality control, significant differences were observed between institutions that regularly conducted quality control of stroke reperfusion therapy nursing and those that organized regular training sessions for nurses in this area ( P<0.05) . Conclusions:While nursing practices and quality for stroke reperfusion therapy in Beijing are progressing, there are disparities in regional development. There is a high demand for specialized stroke nursing and targeted technical training.

Objective To investigate the regulatory effect of Bupi Yichang pill(BPYCP)on CD4+T cell subsets of ulcerative colitis(UC)mice.Methods Forty-eight C57BL/6 mice were randomly divided into 4 groups:the control group(n=10),the model group(DSS group,n=13),the model +BPYCP group(DSS+BPYCP group,n=13)and the model+ mesalazine(5-ASA)group(DSS+5-ASA group,n=12).The mouse UC model was induced by 2.5%dextrosan sulfate(DSS)solution.The DSS+BPYCP group and the DSS+5-ASA group were given BPYCP or 5-ASA for 2 weeks,respectively,and fecal viscosity and blood in stool were observed.The colon length was measured.Colonic mass index and unit colonic mass index were calculated.Hematoxylin-eosin(HE)staining was used to observe pathological changes of colon and to score the pathological tissue damage.The level of CD4+T cell subsets in mesenteric lymph nodes was detected by flow cytometry.The expression levels of cytokines interferon-γ(INF-γ),interleukin(IL-4),IL-17A,IL-10 and IL-21 secreted by CD4+T cell subsets in colon tissue were detected by ELISA.Real-time fluorescence quantitative PCR was used to detect colon tissue CD4+T cell subset nuclear transcription factors,mRNA expression levels of T-frame protein 21(T-bet),GatA-binding protein 3(GATA-3),retinoa-associated nuclear orphan receptor γt(RORγt),B cell lymphoma-6(Bcl-6)and Foxp3 in rats.Results Compared with the DSS group,the diarrhea and hematostoecium symptoms of UC mice in the DSS+BPYCP group and the DSS+5-ASA group were significantly improved,body weight and colon length of mice were increased,and colon mass,colon mass index and unit colon mass index were decreased(P＜0.05).The mucosal epithelium was more complete than that in the DSS group,and gland arrangement was more regular.The inflammatory cell infiltration was less,and the pathological tissue damage score was significantly decreased(P＜0.01).The proportion of Th2 cells in mesenteric lymph nodes was decreased,the proportion of Th17 cells and the level of IL-17A were decreased,and the mRNA levels of T-bet,GATA-3,RORγt and Bcl-6 in colon tissue were decreased(P＜0.05).In the DSS+BPYCP group,the proportion of Th1 cells decreased,the proportion of CD4+CD25+Treg cells,CD4+CD25+Foxp3+Treg cells and the level of IL-10 increased,and the proportion of CD4+CXCR5+Tfh cells and the level of IL-21 decreased.The level of Foxp3 mRNA increased(P＜0.05).The proportion of Th1 cells and the level of IFN-γ were decreased in the DSS+5-ASA group(P＜0.05).Conclusion BPYCP may alleviate UC by remodeling the homeostasis of CD4+T cell subpopulations.

OBJECTIVE To investigated the anti-de-pressant effects of the fruit Areca catechu L.(ACL)and elucidated its potential underlying mechanism using a rat model of chronic unpredictable mild stress(CUMS).METHODS CUMS was induced in rats to establish a depression animal model for 28 d.According to the baseline sucrose preference,the male rats were divided into six different groups.They were treated with parox-etine hydrochloride,ACL,and water once a day until the behavioral tests were performed.The levels of corticoste-rone(CORT),malondialdehyde(MDA),catalase(CAT),and total superoxide dismutase(T-SOD)in serum were de-tected using a commercial kit,and the concentrations of 5-hydroxytryptamine(5-HT)and dopamine(DA)mono-amine neurotransmitters in the brain tissues were detect-ed by liquid chromatography-tandem mass spectrometry.Doublecortin(DCX)expression in the hippocampal den-tate gyrus(DG)was determined by immunofluorescence,and the relative abundance of brain-derived neurotrophic factor(BDNF),TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β of brain tissues were assayed by West-ern blotting.RESULTS ACL markedly increased sucrose preference,decreased the immobility time,and short-ened the feeding latency of CUMS-induced rats.CUMS induction resulted in marked changes in the contents of the monoamine neurotransmitters(5-HT and DA)in the hippocampus and cortex of brain tissues and the levels of CORT,MDA,CAT,and T-SOD in serum,whereas ACL administration alleviated these considerable changes.ACL promoted DCX expression in DG and increased the protein levels of BDNF,TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β in the brains of CUMS-induced rats.CONCLUSION Our results indicated that ACL may improve depression-like behaviors in CUMS-induced rats by decreasing the hyperfunction and oxidative stress of the hypothalamic-pituitary-adrenal axis,stimulating hippo-campal neurogenesis,and activating the BDNF signaling pathway.

This article reported a survived case of amniotic band syndrome (ABS) following fetal reduction by radiofrequency ablation. The woman conceived monochorionic diamniotic twin pregnancy spontaneously. Prenatal ultrasound at 24 weeks of gestation indicated twin-twin transfusion syndrome (stage Ⅲ), and radiofrequency ablation for fetal reduction was successfully performed after formal consent. At 28 +6 weeks, ultrasound reexamination revealed significant edema in the left foot of the fetus, with banding around the ankle, as well as the strangulation mark and narrowing rings. Fetal ABS (ⅡB stage) was diagnosed after multidisciplinary consultation. An immediate emergency cesarean section was performed and a live male baby was born. A thin amniotic band could be seen wrapping around the left ankle of the newborn for several rounds, with obvious strangulation marks about 1 cm deep into the skin, and significant edema on the dorsum and sole of the foot, and the submalleolus area. The amniotic band was released at once, and the edema faded gradually after surgery. After a follow-up of 28 days, the lower limbs of the newborn became normal.

The perception of motion is an important function of vision. Neural wiring diagrams for extracting directional information have been obtained by connectome reconstruction. Direction selectivity in Drosophila is thought to originate in T4/T5 neurons through integrating inputs with different temporal filtering properties. Through genetic screening based on synaptic distribution, we isolated a new type of TmY neuron, termed TmY-ds, that form reciprocal synaptic connections with T4/T5 neurons. Its neurites responded to grating motion along the four cardinal directions and showed a variety of direction selectivity. Intriguingly, its direction selectivity originated from temporal filtering neurons rather than T4/T5. Genetic silencing and activation experiments showed that TmY-ds neurons are functionally upstream of T4/T5. Our results suggest that direction selectivity is generated in a tripartite circuit formed among these three neurons-temporal filtering, TmY-ds, and T4/T5 neurons, in which TmY-ds plays a role in the enhancement of direction selectivity in T4/T5 neurons.
Animals ; Neurites ; Drosophila ; Neurons ; Connectome