Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording; this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.
Animals ; CA1 Region, Hippocampal/physiology* ; Male ; Association Learning/physiology* ; Neuronal Plasticity/physiology* ; Cues ; Memory/physiology* ; Synapses/physiology* ; Conditioning, Classical/physiology* ; Excitatory Postsynaptic Potentials/physiology* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Rats ; Optogenetics

Smoking is a well-established risk factor for periodontitis, yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood. Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution, offering new opportunities to investigate these mechanisms. In this study, we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals, including those with periodontitis, those with smoking-associated periodontitis, and healthy controls. Our analysis revealed that smoking disrupts the epithelial barrier integrity, induces fibroblast alterations, and dysregulates fibroblast-epithelial cell communication, thereby exacerbating periodontitis. The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact, which further promotes the progression of smoking-induced periodontal disease. Importantly, we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype, alleviated epithelial inflammation, and reduced alveolar bone resorption. These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial-macrophage interaction as a therapeutic strategy. Furthermore, this study establishes an essential information resource for investigating the effects of smoking on periodontitis, providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.
Humans ; Gingiva/cytology* ; Smoking/adverse effects* ; Male ; Periodontitis/pathology* ; Single-Cell Analysis ; Female ; Adult ; Middle Aged ; Macrophages ; Fibroblasts ; Endothelial Cells ; Case-Control Studies ; Chemokine CXCL12/metabolism*

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Aim To investigate the predictive value of the Murray law-based quantitative flow ratio(μQFR)after target vessel pretreatment for vascular-related adverse events in patients with de novo coronary lesions treated with drug-coated balloon.Methods This retrospective study included 223 lesions from 223 patients who underwent drug-coated balloon-only strategy and completed 2-year clinical follow-up.Coronary angiographic images of target vessels pre-procedure,post-balloon and post-procedure were collected,and analyzed using a novel Murray's law-based algorithm.The μQFR analysis of each target vessel included not only the μQFR value of the target vessel,but also the length of the target vessel,the degree of vessel diameter stenosis,the reference lumen diameter,the minimum lumen diameter and blood flow velocity.The primary endpoint was defined as the postoperative vessel-oriented composite endpoint(VOCE).Results During the2-year clinical follow-up period,a total of 25 patients(11.2%)experienced VOCE events.Com-pared with the control group,patients with VOCE events after pretreatment showed a decrease in μQFR(P<0.001).Multivariate Logistic analysis showed that a lower target vessel μQFR after pretreatment(OR=0.931,95%CI:0.894～0.969,P<0.001)was an independent predictor of VOCE events.ROC curve analysis showed that the cut-off value for predicting 2-year VOCE events using preprocessed μQFR was 0.83(95%CI:0.727～0.840),with a sensitivity of 72.7%and a specificity of 84.0%(AUC=0.773,95%CI:0.676～0.870,P<0.001).Survival analysis showed that compared with patients with μQFR>0.83,patients with μQFR≤0.83 had a significantly higher incidence of VOCE events at 1 and 2 years,increasing to 3.909 times(16.9%vs.4.6%,HR=3.909,95%CI:1.539～9.930,P=0.004)and 2.867 times(19.7%vs.7.2%,HR=2.867,95%CI:1.301～6.316,P=0.009).After adjusting for potential con-founds,patients with pretreated μQFR≤0.83 had a 2.567 times in 2-year incidence of VOCE events(HR=2.567,95%CI:1.151～5.727,P=0.021)and a 3.712 times in 1-year incidence of VOCE events(HR=3.712,95%CI:1.478～9.810,P=0.006)compared to patients with good pretreatment.Conclusions For patients with in situ coronary artery disease,a lower μQFR after pretreatment increases the risk of postoperative adverse clinical events.μQFR≤0.83 may be used to evaluate the effectiveness of lesion pretreatment.

Objective:To investigate the effects of intravenous lidocaine infusion (IVLI) on the quality of intraoperative neurophysiologic monitoring (IONM) in patients with thyroid tumor.Methods:A prospective randomized controlled study was conducted. A total of 60 patients with thyroid tumor undergoing thyroidectomy in the First Clinical Medical College of Shanxi Medical University between September 2022 and May 2023 were selected. According to the random number table method, all patients were divided into the lidocaine group and the control group, 30 cases in each group. The patients in the lidocaine group were continually given IVLI during the operation and the patients in the control group were continually given the equal 0.9% NaCl solution infusion during the operation. All patients in the 2 groups were induced by the same way of total intravenous anesthesia, and no muscle relaxants were added during anesthesia except the induction dose, and enhanced nerve monitoring tracheal catheter was inserted in the 2 groups. According to the standardized procedure of IONM, the electrode impedance values were measured at the time of eliciting the V1 and V2 signals from the vagus nerve, respectively, and the difference value was defined as the drop in the aggregate impedance level (DAIL). DAIL, perioperative hemodynamic parameters and postoperative recovery quality were compared between the 2 groups.Results:There were no statistically significant differences in the baseline data, operation time, intraoperative dosage of propofol and remifentanil between the 2 groups (all P > 0.05). Compared with the control group, the lidocaine group had a higher proportion of patients with DAIL<50% [80.0% (24/30) vs. 40.0% (12/30), χ2 = 10.00, P = 0.002], a lower hemodynamic fluctuation during extubation [mean arterial pressure: (95±6) mmHg (1 mmHg = 0.133 kPa) vs. (104±7) mmHg, t = 31.00, P < 0.001; heart rate: (73±5) times/min vs. (92±6) times/min, t = 172.58, P < 0.001], a lower visual analog score 24 h after surgery [(2.0±0.7) scores vs. (3.7±0.8) scores, t = -8.86, P < 0.001], a higher score of quality of recovery-15 scale [(127±11) points vs. (118±13) points, t = 2.92, P = 0.005]. Conclusions:IVIL can improve the quality of IONM in patients with thyroid tumor during surgery, reduce perioperative hemodynamic fluctuation and improve postoperative recovery quality of patients.

Objective To explore the protective effect of 7,8-dihydroxyflavone(7,8-DHF)on the retina of diabetic rats and its mechanism.Methods A total of 18 SPF-grade male Sprague-Dawley(SD)rats were selected and randomly divided into three groups:the normal group,the model group,and the experimental group,with six rats in each group.Rats in the normal group were fed with a normal diet,while those in the remaining two groups were fed with a high-fat emulsion through oral gavage continuously for 2 weeks to establish a diabetes model.Rats in the experimental group were provided with 7,8-DHF(5 mg?kg-1)by continuous intraperitoneal injection,while those in the normal and model groups were provided with an equal volume of normal saline.The rats in all groups received intervention once a day for 2 weeks.The changes in the body mass and fasting blood glucose(FBG)were observed before and after modeling.Besides,the changes in the retina of rats in each group were observed by fundus fluorescence angiography(FFA)after 2 weeks.Moreo-ver,the changes and apoptosis of retinal neuronal cells were detected by hematoxylin and eosin(HE)staining,CD31 im-munofluorescence,and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays.Results After 2 weeks of continuous intervention,compared with the normal group,the body mass of rats in the model and experimental groups decreased(both P＜0.05),and the FBG increased significantly(both P＜0.05);compared with the model group,the experimental group showed an increase in the body mass(P＜0.05)and a decrease in the FBG(P＜0.05).The fundus photography and FFA of rats in the three groups did not reveal any fundus features of diabetic retinopathy.The HE staining results showed that the retina of rats in the normal and experimental groups was structurally intact,with neatly arranged cells and uniform thickness;the retinal structure of rats in the model group remained clear.However,the thickness of the inner layers of the retina of rats in the model group was thinner compared with the normal and experimental groups,exhibi-ting significant differences(both P＜0.05).The CD31 immunofluorescence assay results indicated that the CD31 immuno-fluorescence intensity values of rats in the three groups were roughly comparable,without significant differences(all P＞0.05).The TUNEL assay results suggested that the apoptosis of retinal neurons increased in rats in the model group com-pared with the normal group,exhibiting significant differences(P＜0.001);compared with the model group,the apoptosis of retinal neurons of rats in the experimental group decreased significantly,displaying significant differences(P＜0.001).Conclusion The apoptosis of retinal neurons in diabetic rats may precede vascular endothelial cell injury.7,8-DHF can improve the body mass,decrease the blood glucose level,and protect the retinal neurons in diabetic rats.

Luteolin is a natural flavonoid compound exists in various fruits and vegetables. Recent studies have indicated that luteolin has variety pharmacological effects, including a wide range of antidepressant properties. Here, we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power. Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin. Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets. The antidepressant effects of luteolin may involve promoting intracellular noradrenaline (NE) uptake; inhibiting 5-hydroxytryptamine (5-HT) reuptake; upregulating the expression of synaptophysin, postsynaptic density protein 95, brain-derived neurotrophic factor, B cell lymphoma protein-2, superoxide dismutase, and glutathione S-transferase; and decreasing the expression of malondialdehyde, caspase-3, and amyloid-beta peptides. The antidepressant effects of luteolin are mediated by various mechanisms, including anti-oxidative stress, anti-apoptosis, anti-inflammation, anti-endoplasmic reticulum stress, dopamine transport, synaptic protection, hypothalamic-pituitary-adrenal axis regulation, and 5-HT metabolism. Additionally, we identified insulin-like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor alpha (ESR1), and epidermal growth factor receptor (EGFR) as potential targets, luteolin has an ideal affinity for these targets, suggesting that it may play a positive role in depression through multiple targets, mechanisms, and pathways. However, the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.

Objective:To investigate the clinical utility of functional near-infrared spectroscopy (fNIRS) in evaluating cerebral function in neonates with hypoxic-ischemic encephalopathy (HIE).Methods:This was a case-control study. Fifteen neonates with moderate to severe HIE who were admitted to the Department of Neonatal Medical Center, Children's Hospital of Fudan University from March 2023 to August 2024 and completed fNIRS testing were selected as the HIE group, and 15 full-term infants without neurological diseases and completed fNIRS testing were selected as the control group during the same period. Resting-state fNIRS data were acquired to construct cerebral functional connectivity networks and topological properties were analyzed. Statistical analyses included independent t-tests, Mann-Whitney U tests, analysis of variance, and Chi-square tests. Results:Compared with controls, the HIE group exhibited significantly reduced global functional connectivity strength [0.15 (0.05-0.26) vs. 0.24 (0.13-0.35), Z=－7.66, P<0.001]. Both groups demonstrated small-world network properties, with no intergroup difference (1.17±0.05 vs. 1.14±0.05, t=2.02, P=0.050). The HIE group showed decreased shortest path length (6.22±0.52 vs. 13.74±0.49, t=48.18, P<0.001), global efficiency (0.26±0.04 vs. 0.30±0.05, t=2.50, P=0.018) and normalized shortest path length (1.50±0.07 vs. 1.62±0.22, t=2.43, P=0.020). No differences were observed in the clustering coefficient or local efficiency between the two groups. Regional analysis revealed reduced nodal efficiency in both left (0.30±0.06 vs. 0.35±0.05, t=2.47, P=0.021) and right hemispheres (0.30±0.06 vs. 0.37±0.06, t=2.68, P=0.013) in HIE neonates compared with that of the corresponding hemispheres in the control group. The intra-group comparison showed no statistical significance in node efficiency between the left and right hemispheres (both P>0.05). Conclusion:fNIRS captures functional network signatures in HIE, demonstrating clinical potential for early detection of cerebral dysfunction in neonates with hypoxic-ischemic injury.

Objective:To evaluate the clinical utility of left atrial strain parameters and left atrioventricular global longitudinal strain（LAVGLS）in detecting cardiovascular immune-related adverse events（CV-irAEs）among non-small cell lung cancer patients receiving immune checkpoint inhibitors（ICIs）.Methods:A total of 68 patients with non-small cell lung cancer were prospectively enrolled in Tianjin Medical University Cancer Institute and Hospital from October 2023 to October 2024. All patients were treated with ICIs for 6 cycles. Electrocardiogram，cardiac serological markers and echocardiography were examined before medication（T0 stage），4 cycles after medication（T1 stage）and 6 cycles after medication（T2 stage），respectively. According to the guidelines of the American Society of Clinical Oncology，all patients were divided into the CV-irAEs group（ n=14）and the No-CV-irAEs group（ n=54）. AFI software and 4D Auto LAQ software were used to calculate LVGLS，left atrial reservoir longitudinal strain（LASr），LAVGLS and a series of left atrial parameters. Cox proportional hazards regression model was applied to find the risk factors for the occurrence of CV-irAEs. ROC curve was applied to analyze the diagnostic efficiency of these parameters for CV-irAEs. Results:Fourteen patients（20.6%）developed CV-irAEs after T2 stage. After ICIs treatment，LVGLS，LASr and LAVGLS decreased in both groups，LVGLS，LASr and LAVGLS decreased more significantly in the CV-irAEs group than those in the No-CV-irAEs group（ P=0.038，0.047，0.005）. Left ventricular ejection fraction（LVEF）decreased in the CV-irAEs group at the same time（ P=0.003）. Cox multivariate analysis showed that ΔLAVGLS（the difference between stage T0 and stage T2）was a risk factor for CV-irAEs（ HR：1.395， P=0.019）. ROC curve analysis showed the area under the curve of LVGLS，LASr，LAVGLS，ΔLVGLS，ΔLASr，ΔLAVGLS，and LVEF at the T2 stage for diagnosis of CV-irAEs were 0.68，0.67，0.75，0.79，0.73，0.82，and 0.72，respectively. Conclusions:Decline of LAVGLS is a risk factor for CV-irAEs in patients with non-small cell lung cancer receiving ICIs and can be used for early detection of CV-irAEs. LASr has potential diagnostic value for CV-irAEs，but it is less valuable than LVGLS and LAVGLS.

Since the introduction of monoamine oxidase and monoamine neurotransmitter reuptake inhibitors for the treatment of major depression in the 1950s, their strengths and limitations have been fully and accurately determined. Therefore, the development of novel drugs for the treatment of depression has become a priority for researchers who aim to address treatment resistance and improve patient outcomes. Panax ginseng C. A. Mey (P. ginseng, Ren Shen) is a Chinese medicine used to treat neurological and psychiatric disorders. Numerous studies have shown that ginsenosides, the primary active constituents of P. ginseng, exert a wide range of effects on the central nervous system. Recent studies have demonstrated that ginsenosides possess significant antidepressant properties in animal models. Ginsenosides, such as Rb1 and Rg1, are steroidal molecules, and steroid derivatives have been successfully used in anesthesia, epilepsy, and more recently, postpartum depression treatment. Based on these findings, ginsenosides are promising candidates for the treatment of depression. This raises the following question: What are the prospects of using ginsenosides to treat depression? To gain a clearer understanding, this review provides a comprehensive analysis of recent research on the antidepressant potential of ginsenosides, along with insights and suggestions for future development in this field.